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Neutropenia and agranulocytosis (N&A) are relatively rare, but potentially fatal adverse drug reactions (ADR). This study presents cases of N&A related to one or more antipsychotic drugs (APDs) in psychiatric inpatients. Data on APD utilization and reports of N&A caused by APDs were analyzed by using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2016. 333,175 psychiatric inpatients were treated with APDs for schizophrenia and other indications during the observation period. A total of 124 cases of APD-induced N&A were documented, 48 of which fulfilled the criteria for agranulocytosis, corresponding to a rate of 0.37, respectively, 0.14 in 1000 inpatients treated with APDs. Neutropenia was more often detected in women, whereas there was no difference regarding sex in cases of agranulocytosis. Clozapine had the highest relative risk for inducing N&A and was imputed alone as a probable cause of N&A in 60 cases (1.57‰ of all patients exposed). Perazine showed the second highest relative risk with 8 cases and an incidence 0.52‰, followed by quetiapine (15 cases resp. 0.23‰ of all patients exposed) and olanzapine (7 cases; 0.13‰ of all patients exposed). N&A most often occurred during the first 3 months of treatment. Overall N&A are severe and potentially fatal complications that can occur during treatment with APDs. The results from this study largely agree with the currently available literature, highlighting the positive effects of alertness and established appropriate monitoring.

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OBJECTIVES: Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium. METHODS: This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics. RESULTS: A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID. CONCLUSIONS: With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

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Galactorrhea is a well-known adverse drug reaction (ADR) of numerous antipsychotic drugs (APD) and is often distressing for those affected. Methodological problems in the existing literature make it difficult to determine the prevalence of symptomatic hyperprolactinemia in persons treated with APDs. Consequently, a large sample of patients exposed to APDs is needed for more extensive evaluation. Data on APD utilization and reports of galactorrhea caused by APDs were analyzed using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2015. 320,383 patients (175,884 female inpatients) under surveillance were treated with APDs for schizophrenia and other indications. A total of 170 events of galactorrhea caused by APDs were identified (0.97 cases in 1000 female inpatient admissions). Most cases occurred during the reproductive age with the highest incidence among patients between 16 and 30 years (3.81 cases in 1000 inpatients). The APDs that were most frequently imputed alone for inducing galactorrhea were risperidone (52 cases and 0.19% of all exposed inpatients), amisulpride (30 resp. 0.48%), and olanzapine (13 resp. 0.05%). In three cases, quetiapine had a prominent role as a probable cause for galactorrhea. High dosages of the imputed APDs correlated with higher rates of galactorrhea. Galactorrhea is a severe and underestimated condition in psychopharmacology. While some APDs are more likely to cause galactorrhea, we identified a few unusual cases. This highlights the importance of alertness in clinical practice and of taking a patient's individual situation into consideration.

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In view of the current coronavirus disease 2019 (COVID-19) pandemic, patient care, including that of psychiatric patients, is facing unprecedented challenges. Treatment strategies for mental illness include psychotherapy and psychopharmacological interventions. The latter are associated with a multitude of adverse drug reactions (ADR); however, they may currently represent the preferred treatment due to restrictions regarding patient care (i.e. social distancing). Direct contact to patients may have to be reduced in favor of telephone calls or video conferences, so that new techniques in diagnosing and treating patients have to be established to guarantee patient safety. Patients should be extensively informed about relevant ADRs and physicians should actively ask patients about the timely recognition of ADRs. The use of psychotropic drugs may lead to an increased risk of developing ADRs, which are considered to be particularly unfavorable if they occur simultaneously with an acute infection or may even lead to an increased risk of infection. These include respiratory depression, agranulocytosis, intoxication by inhibition of metabolizing enzymes and venous thromboembolism, each of which may be associated with potentially fatal consequences; however, physicians should simultaneously ensure adequate efficacy of treatment, since the ongoing crisis may lead to a worsening of preexisting mental illnesses and to a surge in first onset of psychiatric disorders.

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The elevation of creatine kinase (CK) levels without neuroleptic malignant syndrome has been reported for several antipsychotics. We present here 4 cases with CK elevation induced by amisulpride, which have been registered for the German pharmacovigilance project, Arzneimittelsicherheit in der Psychiatrie (AMSP). The magnitude of the CK elevation ranged between 1, 498 IU/L and 21,018 IU/L. All 4 patients reported myalgia. In each case CK returned to normal after amisulpride discontinuation. In the fourth case, fluids were administered intravenously in order to prevent acute renal failure. None of the cases showed deterioration of renal function. Finally, we present recommendations for clinical practice.

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Based on a careful literature search a review is presented of the history, background, concepts and current use of comedication and polypharmacy in psychiatry. The pros and cons of comedication and polypharmacy are presented, as well as their apparent increase in recent times. Possible reasons for the increase of comedication/polypharmacy are described. Both the potential advantages as well as the potential risks are discussed. The one sided view that all comedication/polypharmacy is nothing but problematic is questioned. Comedication/polypharmacy seems to be, among others, the current answer to the well-known limited efficacy and effectiveness of current monotherapy treatment strategies.

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This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

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RATIONALE: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. OBJECTIVE: This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. RESULTS: Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed--the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. CONCLUSIONS: The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.

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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.

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INTRODUCTION: Patients on levodopa therapy frequently require additional antipsychotic pharmacotherapy. However, consideration must be given to antagonistic interactions on dopamine receptors between levodopa and antipsychotics, and efficacy and safety of such combinations. We therefore aimed to explore the practice and rationale of coprescription between levodopa and antipsychotics in psychiatric patients. METHODS: A descriptive retrospective study based on cross-sectional prescription data repeatedly collected from psychiatric inpatients through the international Drug Safety in Psychiatry (AMSP) program between 1994 and 2008 was undertaken. RESULTS: Within a population of 84 596 psychiatric patients the prevalence of levodopa therapy was 1.0% (n=886). Among those patients on levodopa therapy 59.6% (n=528) also received antipsychotics. Quetiapine coprescription increased after its first marketing in 2000 to 45.9% in 2008. Coprescription of clozapine and olanzapine decreased from up to 25 and 22%, respectively, before to less than 10% after the introduction of quetiapine. Coprescribing of other antipsychotics remained approximately stable with average prevalences between 6 and less than 1%. DISCUSSION: Quetiapine has now replaced clozapine as the most frequently coprescribed neuroleptic in psychiatric patients with levodopa therapy. This is in accordance with recent data indicating a low potential for clinically relevant interactions with levodopa and efficacy against psychosis in levodopa-treated patients. The combined use of antipsychotics other than quetiapine and clozapine with levodopa is less common and generally not supported by appropriate evidence.

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In order to improve medication safety, more epidemiological data on the prevalence and clinical relevance of drug interactions are required. We developed an interface for mass analysis using the Clinical Decision Support Software (CDSS) MediQ and a multidimensional classification (Zurich Interaction System (ZHIAS)) incorporating the Operational Classification of Drug Interactions (ORCA). These were applied to 359,207 cross-sectional prescriptions from 84,607 psychiatric inpatients collected through the international AMSP program. MediQ issued 2,308 "high" and 71,112 "average" danger interaction alerts. Among these, after ORCA reclassification, there were 151 contraindicated and 4,099 provisionally contraindicated prescriptions. The ZHIAS provided further detailed categorical information on recommended management and specific increased risks (QTc prolongation being the most frequent one) associated with interactions. We developed a highly efficient solution for the identification and classification of drug interactions in large prescription data sets; this solution may help to reduce the frequency of overalerting and improve acceptance of the efficacy of CDSS in reducing the occurrence of potentially harmful drug interactions.

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We report the case of a patient with schizophrenia, who experienced agranulocytosis during clozapine treatment, followed by bronchopulmonal infection and Guillain-Barré syndrome. The case was recorded within the German surveillance project "drug safety in psychiatry" (AMSP).

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BACKGROUND: In many cases, patients with personality disorders currently receive psychopharmacological treatment as well as psychotherapy. Empirically oriented studies of outcome and efficacy are still rare, and clinical practice is still dominated by a symptomatic and rather pragmatic approach. AIM: This study provides empirical insight into the reality of psychopharmacological practice in psychiatric institutions in German speaking countries. METHOD: The use of psychotropic drugs in patients with personality disorders is demonstrated using the data base of the AMSP drug safety program. Recent changes are shown by comparing results from 1996 and 2003. RESULTS: Our data show a symptom-driven, polypragmatic, and often off-label use of psychotropic drugs in personality disorders.

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The goal of the multicenter drug surveillance project AMSP ("Arzneimittelsicherheit in der Psychiatrie") is the monitoring, assessment and analysis of adverse drug reactions (ADR) of psychopharmalogical drugs. We report about a 23 year-old patient with a depressive episode. He developed severe pseudohallucinations under a treatment with moclobemide. The symptoms occur 6 days after starting the medication and decline within two days after stopping moclobemide. The term "pseudohallucinations" is discussed controversially but still of high interest.

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The AMSP (Arzneimittelsicherheit in der Psychiatry) study is a drug safety program that ensures the continuous assessment of severe adverse drug reactions (ADR) in psychiatric inpatients under the natural conditions of routine clinical treatment. It developed out of the preceding drug surveillance study AMUP (Arzneimittelüberwachung in der Psychiatrie). Currently 35 hospitals participate in the study. This paper describes the methods of the AMSP, gives detailed definitions of ADRs assessed to be "severe," and discusses the implications of these definitions and the methodological approach for evaluating the AMSP data. In addition, some overall data compiled on ADR rates from 1993 to 2000 are given.

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Adverse drug reactions must be monitored, beginning with the development of a new drug, and continuing throughout its complete life cycle. During these various stages, different methods are necessary. This paper describes the advantages and disadvantages of common methods of collecting data on adverse drug reactions after a drug has been approved. We then concentrate on two drug surveillance projects, the Prescription Event Monitoring (PEM) of the Drug Surveillance Research Unit and the AMSP Project ("Arzneimittelsicherheit in der Psychiatrie", Drug Safety in Psychiatry). AMSP is compared to cohort studies and spontaneous reporting systems on the one hand, and the specialised PEM project, on the other. The possible influence of various sources of bias is critically analysed.

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From 1979 to 1989 the AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie) was conducted in two psychiatric hospitals in Germany with the aim to provide a systematic and standardized assessment of all adverse reactions to psychotropic drugs under conditions of routine practice. A total of 60.7 % of patients experienced at least one adverse drug reaction (ADR) with probable or definite causality during their stay in the hospital; 37.1 % of patients exhibited ADRs that had some therapeutic impact on further treatment. ADRs that led to drug discontinuation were observed in 8.6 %. This rate ranged from 9.5 to 5.1 % for haloperidol and perazine, the most common neuroleptics at that time; sedating antidepressants (AD) rated lower than non-sedating (amitriptyline 5.1 %, clomipramine 10.4 %). Lithium salts, antiparkinson drugs, and benzodiazepines were associated with considerably lower rates of ADRs than neuroleptics or antidepressants. Severe ADRs occurred in 1.4 % of exposed patients (e. g., toxic delirium, grand mal seizures, malignant neuroleptic syndrome, or agranulocytosis). The AMUP data suggest that administration of psychotropic drugs in psychiatric hospitals at that time was a safe, but also inconvenient treatment for many patients due to a wide range of bothersome side effects that compromised patient compliance. The data can serve as a reference base for comparisons with newer compounds introduced to the market over the last decade such as serotonin reuptake inhibitors (SSRIs) and other new AD, atypical neuroleptics, or other new generation psychotropic drugs.

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