[Show abstract][Hide abstract] ABSTRACT: Background:
Several studies have analyzed prescription patterns for bipolar disorder, but few have for acute mania. Treatment strategies in this complex domain change over time and do not always follow evidence-based guidelines.
Prescription data of in-patients suffering from acute mania in the time period from 2005 to 2012 were obtained from the database of the Drug Safety Program in Psychiatry (Institut für Arzneimittelsicherheit in der Psychiatrie; AMSP). Data were collected on two index dates per year. Changes over time were analyzed comparing the time periods 2005/06 and 2011/12.
Among 1650 patients (mean ±SD; age: 48.9±14.91 years; 53.1% females) 54.1% received anticonvulsants, 74.5% second-generation antipsychotics (SGAs), 17.8% first-generation antipsychotics (FGAs), 29.1% lithium, 44.1% benzodiazepines and 14.5% antidepressants. Prescription of SGAs increased from 70% to 79% (p=0.005), while prescription of FGAs and anticonvulsants decreased from 19% to 13% (p<0.05) and 59% to 46% (p<0.001), respectively. Only 30% of patients received monotherapy with one mood stabilizer. We observed an impact of gender, age and psychotic symptoms on treatment strategy. 36.8% of the women≤40 years received valproate.
Follow-up data are missing and no differentiation between acute and maintenance treatments could be made due to the cross-sectional design. Additionally, our findings do not necessarily translate to outpatients or to other countries.
Combination therapies represent standard clinical practice. Though many results reflect clinical necessity, the high number of antidepressant prescriptions or valproate use in women of child-bearing age should be judged critically. Further prospective studies should focus on real-world prescription practice in acute mania to evaluate efficacy and safety of common practice. This paper is dedicated to Prof. Dr. Hanns Hippius on the occasion of his 90th birthday.
No preview · Article · Nov 2015 · Journal of Affective Disorders
[Show abstract][Hide abstract] ABSTRACT: A 75 year-old patient developed increasing gait disturbance and intermittent paresthesia during first time treatment with mirtazapine. Primarily, these symptoms were suspected to represent a somatic syndrome caused by depression and antecedent lumbar pain syndrome accompanied by multiple disk herniations. Electrophysiological diagnostics however revealed distal symmetrical sensorimotor axonal polyneuropathy. After discontinuation of mirtazapine, the symptoms remitted completely, clinically and electrophysiologi-cally. The case was documented and discussed in the context of the pharmacovigilance project AMSP (Drug safety in psychiatry). To our best knowledge, this is the first published case report of electrophysiological documented mirtazapine-asso-ciated polyneuropathy as adverse drug reaction (ADR). This case shows that it is important to pay attention also to rather non-specific symptoms like paresthesia, vertigo or gait disturbances during pharmacotherapy.
[Show abstract][Hide abstract] ABSTRACT: Suicidal thoughts and suicidal behaviour are an often discussed, but rare adverse event of a treatment with selective serotonin reuptake-inhibitors. The following case report shows the importance of the alertness of this side effect. A 40 year old man received 50 mg sertraline daily. After three days, he collapsed for unknown reasons and quit medication. On the two following days he developed ego-dystonic suicidal thoughts that felt very different from the known, depression-like suicidal thoughts he experienced 15 years ago.
[Show abstract][Hide abstract] ABSTRACT: A 41 year old female patient developed during antidepressive therapy with selective serotonin reuptake inhibitor sertraline an extremely disturbing urinary incontinence when the dose was increased from 100 mg to 150 mg. The medication was given because of a recurrent depressive disorder. The patient suffered also from alcohol dependence, polysubstance abuse and borderline personality disorder. After discontinuation of selective serotonin inhibitor the urinary incontinence disappeared completely and occurred again after rechallenge. An adverse side effect was supposed and discussed within the project Drug Safety in Psychiatry (AMSP) e. V.
[Show abstract][Hide abstract] ABSTRACT: Over the past years, international treatment guidelines have been established for the treatment of anxiety disorders. Nevertheless, little is known as to whether the actual inpatient treatment follows these guidelines. The main goal of this study was to answer the question whether patients with anxiety disorder are treated according to treatment guidelines. A total of 2,573 psychiatric inpatients with the diagnosis of anxiety disorder (920 men, 1,653 women) were identified on the basis of the data of the international drug safety programme in psychiatry AMSP. Of these patients, 25.3 % presented with phobia, 26.6 % with panic disorder, 18.7 % with generalized anxiety disorder (GAD), and 29.4 % with other diagnoses of anxiety. In all of the patients, 12.7 % did not receive any psychotropic medication and 22.9 % were not treated with antidepressants. Only 59.3 % of patients with GAD, 73.9 % of patients with panic disorder, and 52.1 % of patients with phobia were treated according to diagnostic guidelines. The majority (60.3 %) of all patients received one or two psychotropic drugs, and only 3.7 % received five or more psychotropic drugs. In two groups of patients (one group with phobia and one with panic disorder), the annual prescription rate of antidepressants significantly increased over time. The prescription rate for anticonvulsants in patients with GAD increased from 0 % in 1997 to 41.7 % in 2011, and for antipsychotics, from 40.7 % in 1997 to 47.2 % in 2011. In particular, patients with GAD were commonly treated with antipsychotics.
No preview · Article · Aug 2014 · European Archives of Psychiatry and Clinical Neuroscience
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
No preview · Article · Sep 2013 · Psychopharmacology
[Show abstract][Hide abstract] ABSTRACT: 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.
Preview · Article · Sep 2013 · The International Journal of Neuropsychopharmacology
[Show abstract][Hide abstract] ABSTRACT: Hyponatremia is a common phenomenon in psychiatry occurring as an adverse effect to drugs or following polydipsia. We performed a retrospective in-depth analysis of hyponatremia cases in a large unselected population of psychiatric inpatients. During a 3-year period, all cases of hyponatremia were identified among patients admitted to a large psychiatric state and university hospital by the institution's electronic laboratory database. Demographic, treatment-related, and laboratory data were obtained by consecutive chart review, respectively. Hyponatremia occurred in 347 (4.9%) of 7113 cases, of which the majority (78%) displayed only a mild manifestation. Symptoms were recorded in 28.8% of cases, already occurred in mild forms, and comprised gait impairment (45%, including falls), confusion (30%), sedation (26%), and dyspepsia (41%). Age, female sex, nonpsychiatric drug polypharmacy-particularly with thiazides and/or angiotensin-converting enzyme inhibitors-and diagnosis of a mood disorder were associated with more severe hyponatremia, respectively. The proportion of hyponatremic patients treated with venlafaxine, trazodone, carbamazepine, oxcarbazepine, and first-generation antipsychotics, respectively, was significantly higher in the hyponatremia sample than in the normonatremic population. This was, surprisingly, not the case with selective serotonin reuptake inhibitors or any other antidepressant drug class. We found prescription with second-generation antipsychotics to be significantly associated with less severe hyponatremia.Hyponatremia may be mainly attributed to the syndrome of inappropriate antidiuretic hormone secretion, as indicated by decreased serum osmolarity in our sample. Besides old age and female sex, treatment with certain drugs-rather than whole drug classes-carries a substantially increased risk.
No preview · Article · Sep 2013 · Journal of clinical psychopharmacology
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jul 2013 · European Archives of Psychiatry and Clinical Neuroscience
[Show abstract][Hide abstract] ABSTRACT: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years.
Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP.
A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions.
The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.
[Show abstract][Hide abstract] ABSTRACT: Background
Clinical decision support software (CDSS) solutions can automatically identify drug interactions and thereby aim to improve drug safety. However, data on the comparative performance of different CDSS to detect and appropriately classify interactions in real-life prescription datasets is limited.
The aim of this study was to compare the results from two different CDSS analysing the pharmacotherapy of a large population of psychiatric inpatients for drug interactions.
We performed mass analyses of cross-sectional patient-level prescriptions from 84,625 psychiatric inpatients using two CDSS – MediQ and ID PHARMA CHECK®. Interactions with the highest risk ratings and the most frequent ratings were reclassified according to the Zurich Interaction System (ZHIAS), a multidimensional classification that incorporates the OpeRational ClassificAtion of Drug Interactions (ORCA) and served as a reference standard.
MediQ reported 6,133 unique interacting combinations responsible for 270,617 alerts affecting 63,454 patients. ID PHARMA CHECK® issued 5,400 interactions and 157,489 alerts in 48,302 patients. Only 2,154 unique interactions were identified by both programmes, but overlap increased with higher risk rating. MediQ reported high-risk interactions in 2.5 % of all patients, compared with 5 % according to ID PHARMA CHECK®. The positive predictive value for unique major alerts to be (provisionally) contraindicated according to ORCA was higher for MediQ (0.63) than for either of the two ID PHARMA CHECK® components (0.42 for hospINDEX and 0.30 for ID MACS). MediQ reported more interactions, and ID PHARMA CHECK® tended to classify interactions into a higher risk class, but overall both programmes identified a similar number of (provisionally) contraindicated interactions according to ORCA criteria. Both programmes identified arrhythmia as the most frequent specific risk associated with interactions in psychiatric patients.
CDSS can be used for mass-analysis of prescription data and thereby support quality management. However, in clinical practice CDSS impose an overwhelming alert burden on the prescriber, and prediction of clinical relevance remains a major challenge. Only a small subset of yet to be determined alerts appears suitable for automated display in clinical routine.
[Show abstract][Hide abstract] ABSTRACT: A 21-year old female patient developed under the initial treatment with trimipramine four days after an increase to a daily dose of 50 mg de novo symptoms of a complex obsessive-compulsive disorder (OCD), which was initially not interpreted as an adverse drug reaction (ADR). After trimipramine was no longer administered, we observed the permanent cessation of OCD symptoms. The relief of symptoms was persistent, even after discontinuation of concomitant medication with sertraline, clomipramine and quetiapine. The case was documented and discussed in the context of the pharmacovigilance project AMSP (drug safety in psychiatry). It represents, to the best of our knowledge, the first published case report of OCD as an ADR associated with trimipramine. We observed in more recent and also in older literature occasional reports of impulse control disorders in patients treated with other antidepressants. In treatment with atypical antipsychotics and clozapine in particular OCD symptoms are also known. Therapists should pay attention in pharmacotherapy with antidepressants on newly emerged OCD symptoms.