ABSTRACT
OBJECTIVE: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Antipsychotic Agents/therapeutic use , Schizophrenia, Disorganized/drug therapy , Schizophrenia, Paranoid/drug therapy , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Antipsychotic Agents/adverse effects , Antipsychotic Agents/classification , Flupenthixol/adverse effects , Schizophrenia/drug therapy , Female , Humans , Male , Observation , Product Surveillance, Postmarketing , Psychiatric Status Rating Scales , Time FactorsABSTRACT
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.
Subject(s)
Antidepressive Agents/adverse effects , Epilepsy, Tonic-Clonic/epidemiology , Inpatients , Pharmacovigilance , Adolescent , Adult , Aged , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Female , Germany , Humans , Male , Middle Aged , Risk , Young AdultABSTRACT
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.
Subject(s)
Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Brief Psychiatric Rating Scale , Diagnostic and Statistical Manual of Mental Disorders , Double-Blind Method , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Psychometrics , Psychotic Disorders/physiopathology , Psychotic Disorders/psychology , Schizophrenia/physiopathology , Schizophrenic Psychology , Severity of Illness IndexABSTRACT
BACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.
Subject(s)
Antipsychotic Agents/therapeutic use , Cognition/drug effects , Piperazines/therapeutic use , Quinolones/therapeutic use , Schizophrenia/drug therapy , Adult , Antipsychotic Agents/adverse effects , Aripiprazole , Attention/drug effects , Humans , Inpatients , Memory/drug effects , Neuropsychological Tests , Piperazines/adverse effects , Psychiatric Status Rating Scales , Quinolones/adverse effects , Reaction Time/drug effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. METHODS: Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. RESULTS: A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. CONCLUSION: The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.
Subject(s)
Antipsychotic Agents/therapeutic use , Cognition Disorders/complications , Cognition/drug effects , Neurons/drug effects , Schizophrenia/complications , Schizophrenia/drug therapy , Acute Disease , Adolescent , Adult , Aged , Aging , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Cognition Disorders/physiopathology , Diagnostic and Statistical Manual of Mental Disorders , Drug Interactions , Humans , Memory/drug effects , Memory Disorders/complications , Memory Disorders/physiopathology , Middle Aged , Schizophrenia/physiopathology , Schizophrenia/therapy , Severity of Illness Index , Time Factors , Young AdultABSTRACT
OBJECTIVE: To review and make recommendations for the definition and presentation of the terms 'response' and 'remission' in schizophrenia. METHOD: Selective review of publications on definitions of response and remission in schizophrenia. RESULTS: When the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) are used for definitions of response, a cut-off of at least 50% reduction of the baseline score should be used for acutely ill, non-refractory patients and a cut-off of at least 25% reduction for refractory patients. When percentage BPRS/PANSS reduction is calculated, the 18/30 points minimum scores meaning 'no symptoms' on the should be subtracted. In addition, responder rates from 0-100% could be presented in a table in steps of 25%. For large and simple practical trials, the Clinical Global Impression scale with suggested improvements could be used 1-7 scale. CONCLUSION: To show how many patients are still symptomatic at the end of study and to show the overall amount of change in both remission and responder criteria should be presented.
Subject(s)
Antipsychotic Agents/therapeutic use , Outcome and Process Assessment, Health Care/statistics & numerical data , Psychiatric Status Rating Scales/statistics & numerical data , Schizophrenia/drug therapy , Schizophrenic Psychology , Antipsychotic Agents/administration & dosage , Clinical Trials as Topic/statistics & numerical data , Drug Resistance , Humans , Psychometrics/statistics & numerical data , Reproducibility of Results , Schizophrenia/diagnosisABSTRACT
We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (-0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat=6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES=-0.39), positive symptoms (ES=-0.48), depression (ES=-0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs and the scarcity of adverse event differences compared with placebo needs to be established.
Subject(s)
Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Randomized Controlled Trials as Topic , Antipsychotic Agents/adverse effects , Humans , MEDLINE/statistics & numerical data , Treatment OutcomeABSTRACT
OBJECTIVES: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. METHODS: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. RESULTS: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. CONCLUSIONS: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.
Subject(s)
Bipolar Disorder/epidemiology , Cognition Disorders/blood , Cognition Disorders/epidemiology , Dysthymic Disorder/epidemiology , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/epidemiology , Social Adjustment , Adult , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Cognition Disorders/diagnosis , Cross-Sectional Studies , Diagnostic and Statistical Manual of Mental Disorders , Drug Therapy/statistics & numerical data , Dysthymic Disorder/diagnosis , Dysthymic Disorder/drug therapy , Female , Humans , Hyperhomocysteinemia/diagnosis , Male , Memory Disorders/diagnosis , Memory Disorders/epidemiology , Neuropsychological Tests , Psychology , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
BACKGROUND: The aim was to systematically integrate the available evidence on psychosocial and demographic factors associated with response prediction to prophylactic lithium. METHOD: Each psychosocial or demographic variable that was related to lithium response in at least one study was examined with respect to response prediction. If several studies were located for the same variable results were integrated using a meta-analytical approach. To account for heterogeneity of primary studies aggregation of results was based on a random-effects model. RESULTS: Out of 27 psychosocial and demographic variables investigated in this review, nine variables were identified as significantly related to outcome under to prophylactic lithium: (1) high social status, (2) social support, (3) good compliance, and (4) dominance may be protective against a recurrence under lithium. In contrast, (5) stress, (6) high expressed emotions, (7) neurotic personality traits, (8) unemployment, and (9) a high number of life events were identified as possible risk factors for poor response. CONCLUSIONS: This systematic review shows a surprisingly high number of psychosocial variables to be related to lithium response. Effect sizes were, however, small to moderate. Many variables should, therefore, be considered simultaneously to predict response.
Subject(s)
Antimanic Agents/therapeutic use , Anxiety Disorders/therapy , Lithium Carbonate/therapeutic use , Neurotic Disorders/therapy , Obsessive-Compulsive Disorder/therapy , Adult , Demography , Female , Humans , Life Change Events , Male , Psychology , Social SupportABSTRACT
A serotonergic dysfunction was suggested to be involved into the biological susceptibility of suicidal behaviour. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is a significant regulating factor in the serotonergic system. Recently the A-6526G, and G-5806T and A-779C polymorphisms of the TPH 1 gene were identified and suggested to be associated with suicidal behaviour, but study results are conflicting. We examined a possible association of the A-6526G, and G-5806T and A-779C polymorphisms with suicide attempts in a sample of 80 alcohol-dependent individuals with a history of at least one suicide attempt. This group was analysed in comparison with 241 alcohol-dependent subjects without such a history. No significant relationship between haplotype and genotype distribution and allele frequencies of these polymorphisms with suicide attempts were detected. Furthermore, no association with number of suicide attempts and TPH haplotypes were found. Our data do not support the hypothesis of A-6526G, G-5806T or A-779C polymorphisms to be associated with suicide attempts in alcohol-dependent individuals.
Subject(s)
Alcoholism/epidemiology , Polymorphism, Genetic/genetics , Suicide, Attempted/psychology , Suicide, Attempted/statistics & numerical data , Tryptophan Hydroxylase/genetics , Adult , DNA Primers/genetics , Female , Genotype , Haplotypes/genetics , Humans , Male , RecurrenceABSTRACT
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.
Subject(s)
Adverse Drug Reaction Reporting Systems , Product Surveillance, Postmarketing , Psychotropic Drugs/adverse effects , Brain Diseases/drug therapy , Brain Diseases/physiopathology , Hospitals, Community , Hospitals, Psychiatric , Hospitals, State , Hospitals, University , Humans , Mental Disorders/drug therapy , Mental Disorders/physiopathology , Psychopharmacology , Psychotropic Drugs/therapeutic useABSTRACT
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.
Subject(s)
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions , Product Surveillance, Postmarketing , Research Design , Case-Control Studies , Cohort Studies , Data Interpretation, Statistical , Drug Monitoring , HumansABSTRACT
A considerable number of new drugs were introduced over the last few years. In this report we analyze to what extent they have come to be used in clinical practice and what changes in drug use have resulted from the availability of the new compounds. For this purpose, data on drug use in 1995 and 2001 assessed at two reference days per year and per hospital within the drug safety program AMSP were compared for 10 hospitals that had been participating in both years. Atypical neuroleptics (NL) were used in 59.9 % of patients on NLs in 2001 (16.7 % in 1995), most frequently olanzapine, risperidone, clozapine, and quetiapine, in this order. Thirty-nine percent of patients still received typical NLs in antipsychotic indication (77.1 % in 1995), and 30.8 % received typical hypnosedative NLs (38.1 % in 1995). SSRIs, other new ADs, and TCAs were used in similar rates in 2001, i. e., in 40.5 %, 37.9 %, and 34.8 % of AD patients, respectively (1995 : 24.2 %, 6.2 %, and 72.3 %, respectively). Mirtazapine was the most common AD in 2001, followed by citalopram, sertraline, and doxepin. Hypnotics were prescribed more frequently in 2001 (17.6 % vs. 11.7 %), mostly BZD agonists at that time, whereas overall anxiolytic use (in approximately 30 %) hardly changed over time. Mood stabilizers and anti-dementia drugs were given comparatively rarely, even in pertinent diagnoses. Polypharmacy was observed in about three-quarters of patients on psychotropic drugs, with a trend towards increasing use over time. Combinations of two NLs, of NL + AD, and of NLs + anxiolytic were most common in both years. Twenty percent of patients on atypical NLs received typical antipsychotic NLs additionally; typical hypnosedative NLs were used along with typical antipsychotics and atypical NLs in 20 % and 22 % of patients, respectively. TCAs and either SSRIs or other new ADs were still the most common AD combinations in 2001. Data were also analyzed according to the main diagnostic categories.
Subject(s)
Adverse Drug Reaction Reporting Systems/trends , Mental Disorders/drug therapy , Psychotropic Drugs/therapeutic use , Adolescent , Adult , Age Distribution , Aged , Depression/drug therapy , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Drug Utilization/trends , Female , Humans , Hypnosis/methods , Male , Mental Disorders/epidemiology , Middle Aged , Multicenter Studies as Topic , Product Surveillance, Postmarketing/methods , Product Surveillance, Postmarketing/trends , Prospective Studies , Psychotropic Drugs/adverse effects , Retrospective Studies , Time FactorsABSTRACT
The goal of the German drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the assessment of severe or new adverse drug reactions (ADRs). Here we report on 53,042 of 122,562 patients treated with antidepressants who were monitored from 1993 to 2000 in 35 psychiatric hospitals in German-speaking countries. The overall incidence of severe ADRs of antidepressants was 1.4 % of exposed patients; when only ADRs rated as probable or definite were considered, a rate of 0.9 % in patients treated with antidepressants was observed. ADR rates were higher for TCAs (imputed in 1.0 % of patients overall, respectively in 0.6 % of patients when only ADs were imputed) and lower for MAO inhibitors and SSRIs (0.7 % for both, respectively 0.3 % and 0.4 %). Within the TCA group there was a difference among clomipramine (2.1 %, respectively 1.0 %), amitriptyline (1.0 %, respectively 0.6 %), and doxepin or trimipramine (both 0.6 %, respectively 0.3 %). With regard to single SSRI, similar rates were observed for paroxetine (0.8 %, respectively 0.5 %) and for citalopram (0.7 %, respectively 0.4 %). Of the new dual-acting antidepressants, venlafaxine ranged at 0.9 %, (respectively 0.5 %) and mirtazapine at 0.6 % (respectively 0.5 %). In particular, TCAs were associated with known risks, such as toxic delirium, grand mal seizures, and hepatic (i. e., increased liver enzymes), urologic (i. e., urinary retention), allergic (i. e., exanthema), or cardiovascular (i. e., mainly orthostatic collapse) reactions. In SSRI-treated patients (non-delirious) psychic and neurological ADRs were most prominent, followed by gastrointestinal, dermatologic, and endocrinological/electrolyte reactions, with agitation, hyponatremia (probably as part of the SIADH syndrome and associated with severe neurologic or psychiatric symptoms in 64 % of all cases), increased liver enzymes, nausea, and the serotonin syndrome as leading unwanted symptoms. Venlafaxine (in the immediate-release formulation) was associated with adverse CNS and somatic symptoms such as severe agitation, diarrhea, increased liver enzymes, hypertension, and hyponatremia. Mirtazapine was mostly connected with increased liver enzymes, cutaneous edema, and collapse, but with no case of significant hyponatremia. For drugs that potently inhibit serotonin uptake, serum sodium concentration should be controlled when applied in high-dose therapy or in vulnerable patients.
Subject(s)
Adverse Drug Reaction Reporting Systems , Antidepressive Agents/adverse effects , Monoamine Oxidase Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Adult , Age Distribution , Aged , Depression/complications , Depression/drug therapy , Depression/epidemiology , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Female , Germany , Humans , Incidence , Male , Middle Aged , Product Surveillance, Postmarketing/methods , Prospective Studies , Sex DistributionABSTRACT
Numerous studies compare side effects or adverse drug reactions (ADRs) of the various typical and newer atypical neuroleptics in patients with schizophrenia. However, these studies, as controlled randomized trials, represent an artificial setting of drug administration and do not easily relate to the "real-life" setting of psychiatric treatment. In contrast, the AMSP drug safety program allows the monitoring of ADRs of all types of psychopharmacological agents in the naturalistic setting of routine clinical practice. In the present study, the data on neuroleptics acquired in the AMSP program from 1993 to 2000 are analyzed. In this period, 86,439 patients treated with at least one neuroleptic agent were monitored. In 1.1 % of the patients severe ADRs occurred. In contrast to the results from controlled trials, atypical neuroleptics caused more severe ADRs than did typical neuroleptics. This result was mainly caused by the high number of severe ADRs in patients treated with clozapine and concerned delirium and non-EPS neurological, gastrointestinal, hepatic, dermatological, hematological, and endocrinological ADRs. Atypical neuroleptics were found to be superior in EPS and urological ADRs. Excluding the data on clozapine, we found typical and atypical neuroleptics to be similar in the occurrence of severe ADRs, although the profiles differ between these two groups as well as between the single substances. Our findings provide valuable information on the type and frequency of ADRs in psychiatric practice, thus enabling differential indication of neuroleptics based not only on the efficacy and tolerability data of controlled trials but also on their differential ADR profile occurring in the "real-life" setting of routine clinical treatment.
Subject(s)
Adverse Drug Reaction Reporting Systems , Antipsychotic Agents/adverse effects , Schizophrenia/drug therapy , Adult , Age Factors , Aged , Depression/drug therapy , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Female , Humans , Inpatients , Liver/drug effects , Liver/enzymology , Male , Middle Aged , Multicenter Studies as Topic , Pharmaceutical Preparations , Product Surveillance, Postmarketing , Prospective Studies , Retrospective Studies , Schizophrenia/physiopathology , Treatment OutcomeABSTRACT
Within the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie), severe adverse drug reactions (ADRs) in psychiatric inpatients are assessed in the naturalistic setting of routine treatment. Currently, 35 psychiatric hospitals and departments are participating. This paper focuses on severe cardiovascular ADRs due to psychotropic medications. Related to the number of patients surveyed (122,562 from 1993 to 2000), these are rare events (68 cases or 0.055 %). Imputed drug classes for probable cases were antidepressants in 0.03 % and neuroleptics in 0.019 %, but other drugs were also involved. Within the group of antidepressants, the risk for a cardiac ADR depends much on the class: SSRIs were never imputed alone, but tricyclic antidepressants were imputed alone in 0.05 %. In the group of antipsychotics, the lowest rate of cardiac ADRs was found for the group of phenothiazines (0.003 %). Cardiovascular risk factors elevated the risk for a cardiac ADR from 0.04 % to 0.14 %. Age as an independent factor did not contribute substantially to the risk for a cardiac ADR. The data of the drug safety program in psychiatry allow some estimate of differential risk rates for cardiac ADRs with different psychotropic drug groups. The results of the project can help clinicians select the appropriate drug for patients at risk to develop cardiac ADRs.
Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Cardiovascular Diseases/chemically induced , Psychotropic Drugs/adverse effects , Adult , Aged , Cardiovascular Diseases/epidemiology , Case-Control Studies , Confidence Intervals , Drug Interactions , Female , Humans , Incidence , Male , Mental Disorders/drug therapy , Middle Aged , Pharmacoepidemiology , Product Surveillance, Postmarketing/methods , Retrospective Studies , Risk FactorsABSTRACT
Within the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie), severe adverse drug reactions (ADRs) are assessed. Currently 35 psychiatric hospitals and departments are participating in detecting severe ADRs. This paper focuses on prolactin-dependent ADRs such as gynecomastia and galactorrhea due to psychotropic medications. Related to the number of patients surveyed (122,562 from 1993 to 2000), these are rare events (0.03 % or 35 cases). Imputed drugs were mostly antipsychotics, but antidepressants were also imputed in single cases. In the group of antipsychotics, relative frequencies of galactorrhea were highest for amisulpride and risperidone and corresponded to the degree of D2 binding. Galactorrhea assessed as "severe" was accompanied by distressing symptoms such as pain, tension, enlargement of breasts, or soaked clothing. The AMSP data contribute to the knowledge on endocrine ADRs by the large number of patients examined and help clinicians select the appropriate drug if their patients have been prone to for these ADRs in the past.
Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Galactorrhea/chemically induced , Psychotropic Drugs/adverse effects , Adult , Female , Follow-Up Studies , Galactorrhea/epidemiology , Humans , Incidence , Male , Mental Disorders/drug therapy , Mental Disorders/physiopathology , Middle Aged , Product Surveillance, Postmarketing , Prolactin/blood , Prospective Studies , Time FactorsABSTRACT
OBJECTIVE: Impulsive traits are key characteristics in a number of psychiatric disorders and are part of the normal behavior spectrum. The BIS-5 is an instrument developed to assess impulsivity. The aim of this study is to evaluate the BIS-5 in two German psychiatric inpatient samples and healthy controls proving the originally proposed four-factor structure as well as convergent and discriminate validity. METHODS: 159 alcohol-dependent subjects and 77 suicidal inpatients were recruited in an University psychiatric hospital. 182 healthy subjects were recruited from town community. BIS-5 items were translated and back-translated. Principal component analysis with oblique rotation was conducted in the whole group. Furthermore, the discriminate and convergent validity of the BIS-5 was evaluated by correlation with other instruments measuring impulsive traits and comparing sample subgroups. RESULTS: A two-factor solution could be identified in this German sample. Alcohol-dependent individuals showed significantly higher factor 1 values compared to suicidal patients. The group of suicidal patients had higher scores in factor 2 compared to controls. Factor 1 correlated most significantly with extraversion-related personality traits while factor 2 showed significant relationships with irritability and neuroticism. CONCLUSIONS: A two-factor solution may be more appropriate in using the BIS-5 scale in German samples. These two factors might reflect different aspects of impulsive behavior and might be useful to characterize impulsive behavior in psychiatric and non-psychiatric samples.