Adverse drug reactions. An epidemiological study at psychiatric hospitals

A drug monitoring system has been established at psychiatric university hospitals in Berlin, Goettingen, and Munich since 1979 in order to investigate adverse reactions to psychotropic drugs. This report describes the system and presents results obtained over 3 years. 504 randomly selected patients were observed by Intensive Drug Monitoring; 75% of them had an adverse drug reaction (ADR) during hospitalization that was assessed as possible, probable, or definite including all grades (I-III) of severity. 5,096 other patients were monitored by Organized Spontaneous Reporting during treatment with psychotropic drugs: ADRs were responsible for drug withdrawal (severity grade III) in about 10% of them. Parkinsonism, psychomotor disturbance, akathisia, delirium, oversedation and increased transaminases were the most frequent ADRs of this kind. The relative frequency of ADRs was calculated, and ADR-profiles established for drugs most frequently withdrawn. The impact of ADRs on ongoing therapy of patients was assessed. Reliable data obtained by drug monitoring systems can be expected to aid in therapeutic decisions in patients with special risks of side effects to psychotropic drugs.     

Psychotropic drug use and polypharmacy in a general hospital

This paper presents the usage of psychotropic drugs by all general inpatients of a Boston teaching and referral hospital on a randomly chosen weekday. Of all surveyed inpatients, 42.8% were receiving at least one psychotropic medication. Sleep medications were the most frequently prescribed class of psychotropic drugs and flurazepam was the most commonly prescribed of all drugs. Phenothiazine and neuroleptics were given to control agitation, pain, or nausea, rather than psychosis. Antidepressants were prescribed without notated justification in the medical record, and if given for depression, were underdosed. Diazepam was the most frequently prescribed antianxiety drug and was the most frequently prescribed psychotropic drug after flurazepam. Psychotropic drug polypharmacy was common, with the average patient receiving seven different drugs. Remedial approaches to this widespread problem are recommended.     

Behavioral symptoms and the administration of psychotropic drugs to aged patients with dementia in nursing homes and in acute geriatric wards

OBJECTIVES: To describe the prevalence of various psychiatric and behavioral symptoms among patients with dementia in nursing homes and acute geriatric wards and to investigate the administration of psychotropic medications to these patients. METHODS: 425 consecutive patients (>70 years) in six acute geriatric wards in two city hospitals and seven nursing homes in Helsinki, Finland, were assessed with an extensive interview, cognitive tests, and attention tests. Of these, 255 were judged to have dementia according to the following information: previous dementia diagnoses and their adequacy, results of CT scans, Mini-mental State Examination (MMSE) tests, Clinical Dementia Scale (CDR) tests, and DSM-IV criteria. Psychiatric and behavioral symptoms were recorded over two weeks for each patient. RESULTS: Psychiatric and behavioral symptoms were very common among patients with dementia in both settings. In all, 48% presented with psychotic symptoms (delusions, visual or auditory hallucinations, misidentifications or paranoid symptoms), 43% with depression, 26% agitation, and 26% apathy. Use of psychotropic drugs was also common: 87% were on at least one psychotropic drug, 66% took at least two, 36% at least three, and 11% four or more psychotropic drugs. Of the patients with dementia, 42% were on conventional antipsychotics, and 34% on anxiolytics despite their known side-effects. Only 13% were on atypical antipsychotics and 3% on cholinesterase inhibitors. The use of selective serotonin reuptake inhibitors (SSRIs) was common (31%) among the patients. A surprising finding was that drugs with anticholinergic effects were also frequently (20%) used. CONCLUSION: Both behavioural symptoms and use of psychotropic drugs are very common among dementia patients in institutional settings. The frequent use of potentially harmful drugs implies a need for education among physicians taking care of these patients.     

Psychotropic drug versus psychotropic drug-update

Psychotropic drugs are not necessarily the drugs of psychiatry. Seventy percent of antidepressants, and 90% of anxiolytics are prescribed by nonpsychiatric physicians. Since psychotropic medications are so frequently employed by nonpsychiatric physicians, e.g., neurologists, primary care physicians, internists, and because large numbers of their patients are concurrently on medical drugs for somatic reasons, the interactions of psychotropic versus medical drugs and psychotropic versus psychotropic drugs as listed below must be understood before primary care physicians or psychiatrists prescribe psychotropic medications, especially to the medically ill. Seventy commonly prescribed psychotropic drugs were examined for their interactions with other psychotropic medications using six reference tools: 1) MEDLINE (PubMed) employing the first generic psychotropic drug name, the second generic psychotropic drug name, and the term "interaction;" 2) Hanston's Drug Interaction Analysis and Management Text (quarterly updated version); 3) Drug Interactions Facts (Facts and Comparisons) (July 2001 quarterly updated version); 4) Micromedex Drug-dex; 5) American Hospital Formulary Service Drug Information; and 6) Food and Drug Administration (MedWatch) (Dear Doctor Letters and new labeling) ( for (1999, 2000, and 2001). The authors recognized that all of the above sources do not necessarily cover the entire information database regarding drug-drug interactions. (Citations regarding children, reports in foreign languages or concerning food, animals, in vitro experiments, analgesics, and naturalistic-herbal or natural products-treatment interactions were excluded).     

Psychotropic drug use in the Boston area. A report from the Boston Collaborative Drug Surveillance Program.

During 1972, adults admitted to general medical and surgical wards in Boston area hospitals were interviewed to determine their use of prescribed psychotropic drugs prior to hospitalization. Patients hospitalized for psychiatric disorders or psychogenic ("functional") disease were excluded. Patients who had taken prescribed drugs that could not be identified were considered nonusers. Of the total sample, 20% gave a histroy of psychotropic drug use. Antianxiety drugs were taken by 15% of the patients and accounted for two thirds of total psychotropic drug use. Hypnotics were taken by another 4% of the sample. Slightly over half of antianxiety and hypnotic drug use was for a year or more. Use was more frequent in patients with potentially chronic medical disorders. The findings, in general, are consistent with other studies employing other methods to investigate the use of psychotropic drugs. Simple studies of use, however, do not provide a sole or adequate definition of treatment option, need, or efficacy.     

The AMUP study for drug surveillance in psychiatry - a summary of inpatient data

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.     

Self-reported bullying in childhood: Relationships with employment in adulthood

Objectives. Hypersensitivity reactions to drugs are not infrequent. A certain of anxiety, aggression or depression should be expected in patients with drug allergies, as they could experience symptoms ranging from mild to life-threatening reactions following consumption of drug. However, a literature search resulted in very limited data. This study was designed to evaluate the psychological status of patients with drug allergy and to assess the relationships between psychological evaluations of the patients and, duration of drug allergy, type of allergic reaction, hypersensitivity reaction of the type of drug involved. Methods. The study group comprised 61 patients (43 F, 18 M), age ranging from 16 to 75 years, with reliable history of drug allergy. A total of 55 healthy subjects (39F, 16M) age ranging from 17 to 70 years served as control group. Assessment tools consisted of Beck Depression Inventory (BDI), and Speilberger's State-Trait Anxiety Inventory (STAI Tx-2). Results. The prevalence of depression and anxiety among patients with drug allergies was not greater than that of the controls. There were no associations between the scores of these psychological assessments and duration of drug allergy, type of allergic reaction, type of drug. Conclusions. Our data suggest that follow-up studies including high numbers of patients and patients with specific and potentially life-threatening clinical pictures of drug allergies are needed to detect clinically relevant associations.     

Psychotropic drug use and correspondence with psychiatric diagnoses in the mental health in the general population survey

OBJECTIVES: The aims of this study were to assess the lifetime prevalence rate of psychotropic drugs use in the French general population and the correspondence between psychotropic drug use and psychiatric diagnoses. METHODS: Data were derived from the multicentric survey mental health in the general population, carried out in 47 French public sites between 1999 and 2003. A face-to-face questionnaire was used to interview a representative sample of French metropolitan subjects, aged 18 and over, noninstitutionalized or homeless. These subjects were recruited using quota sampling for age, sex, socioprofessional and education levels, according to data from the 1999 national French population census. Lifetime use of psychotropic drugs was explored by an open question. Psychiatric diagnoses were identified using the mini international neuropsychiatric interview (MINI). A national database was then constituted by pooling data from all sites, weighted for age, sex, level of education, socioprofessional level and work status, to be representative of the French general population. RESULTS: Of the 36785 individuals included in this study, more than one out of three subjects reported having used at least one psychotropic drug during their life. Anxiolytics were the most commonly used drugs, reported by 19.4% of the sample. The other frequently used psychotropic drugs were antidepressants (11.6%) and hypnotics (9.2%). Nearly half of the subjects with a MINI diagnosis reported no lifetime psychotropic drug use. Among the subjects meeting criteria for a diagnosis of mood disorder, 66.3% used psychotropic drugs. However, less than one out of three subjects with a diagnosis of major depressive disorder used antidepressants while 37.2% reported having used anxiolytics. Less than one out of four subjects with a diagnosis of anxiety disorder used antidepressants while 34.3% used anxiolytics. Among subjects with a diagnosis of anxiety disorder, antidepressants and anxiolytics were the most commonly used drugs for subjects with a diagnosis of panic disorder with agoraphobia (46.4 and 58.1%, respectively). Conversely, these were the treatments used the least by subjects with a diagnosis of generalized anxiety disorder (21.9 and 31.5%, respectively). Only 14.9% of subjects with a psychotic syndrome reported having used neuroleptics. Lastly, the highest proportion of subjects with at least one psychiatric diagnosis was found in mood stabilizer and neuroleptic users. However, one third of mood stabilizer users, a quarter of neuroleptic users and less than half of antidepressant and anxiolytic users presented no psychiatric disorder identified by the MINI. CONCLUSION: This study highlights the high frequency of exposure to psychotropic drugs in the general French population, and the marked inadequacy between the presence or absence of a psychiatric diagnosis and the lifetime presence or absence of a psychotropic drug treatment.     

Allergy to tartrazine in antidepressants

The authors describe five cases of apparent allergy to tartrazine (FD&C yellow dye number 5) in 170 patients exposed to the dye in antidepressants. The frequency of tartrazine sensitivity was much higher than the reported frequency of six in 1,000 persons.     

Prevalence and appropriateness of psychotropic drug use in old age: results from the Berlin Aging Study (BASE)

BACKGROUND: The aim of this epidemiological study is to examine the prevalence and correlates of psychotropic drug use in the very old and to evaluate the appropriateness of psychotropic drug use in very old age. METHODS: Data from the Berlin Aging Study (BASE), a multidisciplinary study of an age- and gender-stratified, randomly selected sample of elderly people living in Berlin are presented. Over-sampling, especially very old men, allows for powerful analyses of this population. All participants went through extensive psychiatric and somatic examinations. Medication intake was assessed by different data sources (interviewing patients and their family physicians, drug inspection at home). Results were brought together in a consensus-conference and research physicians gave operationalized ratings of medication appropriateness. RESULTS: The prevalence of elderly people who were taking at least one psychotropic medication within the 14 days immediately preceding investigation was 29.8%. Of these medications, 68.4% had been taken for longer than one year. There was no effect of age or gender on the scope of psychotropic drug use. Benzodiazepines were taken by 19.8% of the elderly. Antidepressants, neuroleptics and anti-dementia drugs were taken by about 3-4% each. People taking psychotropic drugs had significantly higher levels of psychiatric morbidity, as measured by syndromes and specified diagnoses. Psychotropic drugs were significantly less often judged to be indicated than somatic medications. This is mostly due to benzodiazepines. CONCLUSIONS: Psychotropic drug use is common in old age, but there is no additional increase in usage beyond the age of 70. Intake of psychotropics is mostly oriented at symptoms or syndromes, which explains why benzodiazepines are still the most commonly prescribed psychotropics.     

Psychotropic drug use in older people with mental illness with particular reference to antipsychotics: a systematic study of tolerability and use in different diagnostic groups

OBJECTIVE: The objective of the study was to provide observational clinical data on psychotropic drugs used in older people with mental illness. METHODS: This was an observational, single-centre, one-week prevalence study of psychiatric symptoms, disorders and psychotropic drug use in older with mental illness cared for by the South West people Yorkshire Mental Health NHS Trust (Wakefield Locality), UK. The clinical assessment included completion of the Psychosis Evaluation Tool for Common use by Caregivers. RESULTS: A total of 593/660 older patients with mental illness (mean +/- SD age, 76 +/- 8.1 years were assessed. 44.5% had dementia (excluding vascular dementia) and 33.7% had a mood disorder. Of the total, 20.4% did not receive CNS active medication. Of those receiving CNS active medication approximately half (51.3%) took antipsychotics and 46.2% antidepressants. Of 304 patients taking antipsychotics, 87% took only one medication. However, patients with schizophrenia and related disorders were significantly more likely to be prescribed two or more antipsychotics (p < 0.001). Risperidone was the most frequently prescribed antipsychotic (n = 136, 44.7%). Risperidone doses were significantly lower for patients with dementia and mood disorders than with schizophrenia (p < 0.002). Side-effects from antipsychotics were significantly greater in patients with schizophrenia, suggesting a dose-related effect. Risperidone appeared to be well tolerated in all patients with no evidence of cerebrovascular side-effects in patients taking it. CONCLUSIONS: Psychotropic drugs were commonly used by older people in contact with mental health services. The doses of antipsychotics used in dementia and affective disorders were significantly lower than in schizophrenia. Risperidone was the most commonly used drug in all diagnostic groups including dementia. Despite a relatively large numbers of patients receiving risperidone in this naturalistic study, no serious side-effects were reported or identified. In this paper we focus our findings on antipsychotics in the light of recent advice from the Committee on Safety of Medicines (UK).     

Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders

OBJECTIVE: Bipolar disorders are prevalent major illnesses with high rates of morbidity, comorbidity, disability, and mortality. A growing number of psychotropic drugs are used to treat bipolar disorder, often off-label and in untested, complex combinations. METHODS: To quantify utilization rates for psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan research databases to identify 7,760 persons with ICD-9 bipolar disorder subtypes. Survival analysis was used to estimate times until initial monotherapies were augmented, changed, or discontinued. RESULTS: The most commonly prescribed first drug class was antidepressants (50% of patients), followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%), sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients were receiving monotherapy. Those receiving monotherapy were ranked by initial drug prescribed and percentage of patients (bipolar I and bipolar II): antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and 31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to adding another psychotropic was 2.5-times less than median time to changing the initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median weeks until therapy was changed in any way for 25% of patients was as follows: lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13; and sedatives, 9. CONCLUSIONS: Antidepressants were the first-choice agent twice as often as mood stabilizers. Lithium was sustained longer than monotherapy with other mood stabilizers. Time to augmentation was much shorter than time to change or discontinuation.     

Treatment-resistant depression: when antidepressant drug intolerance may indicate food intolerance

OBJECTIVE: To describe a patient with food intolerance probably contributing to depressive symptoms, intolerance to psychotropic medication and treatment resistance. METHOD: The case vignette and investigatory procedures are detailed. RESULTS: The patient's course improved considerably with an elimination diet. CONCLUSIONS: The prevalence of food intolerance as a contributing factor to depressive disorders requires clarification. Clinicians should be aware of the possible syndrome and that it may be worsened by psychotropic medication.     

Relapse of aggressive and disruptive behavior in mentally retarded adults following antipsychotic drug withdrawal predicts psychotropic drug use a decade later

BACKGROUND: Mental retardation is frequently associated with aggression toward self and others. Antipsychotic medications are frequently used as a major treatment of such aggression. However, national and state policies and guidelines are weighted toward stopping or decreasing the doses of these medications whenever possible, although exceptions are permitted. The purpose of this study was to determine if relapse during or after antipsychotic drug withdrawal in mentally retarded adults predicts continuing antipsychotic drug use an average of a decade later. METHOD: We report here on a 6- to 13-year (average 10-year) follow-up of 151 institutionalized mentally retarded adults. During the period 1990-1997, the subjects had been prescribed antipsychotic medications to treat maladaptive behaviors, primarily consisting of aggression, disruptive/destructive behaviors, or a combination of these. We compared subjects' psychotropic medication profiles in 2003 as they related to outcome during the earlier period. Our goal was to determine if rapid relapse (a clinically significant increase in maladaptive target symptoms, beginning 3 months or less after antipsychotic drug termination or dosage reduction, that was reversed by antipsychotic drug reinstitution or dosage increases) during or after routine withdrawal of an antipsychotic predicted psychotropic drug use in 2003. RESULTS: For those individuals successfully withdrawn from antipsychotic medications, 66.3% (55/83) were still psychotropic drug free in 2003. For those who rapidly relapsed during the period 1990-1997 following antipsychotic drug withdrawal or dosage decreases, only 9.0% (5/55) were psychotropic medication free in 2003. CONCLUSION: These observations support policies and guidelines indicating that attempts to stop treatment with antipsychotic medications in mentally retarded individuals are worthwhile. However, the results also indicate that eventual discontinuation of antipsychotic medications in institutionalized mentally retarded adults who have previously relapsed upon such withdrawal is unlikely to be successful. Rigid adherence to drug withdrawal policies and guidelines in such individuals should be reconsidered.     

Medically induced myopathia

Muscular side effects of various anesthetics, analgetics, antibiotics, antihistaminic drugs, antiretrovirals, cardiotropics, immunosuppressants, lipid-lowering drugs, psychotropic drugs, anticancer drugs, and other substances are more frequent than assumed and are easily overlooked. Clinically, muscular side effects manifest as fatigue, myalgias, persistent or transient weakness, stiffness, intolerance to exercise, psychomotor slowing, muscle cramps, wasting, dyspnea, dysphagia, fasciculations, reduced tendon reflexes, impaired consciousness, myoglobinuria, renal failure, or hyperthermia. Diagnosis of these drug-induced myopathies is based on history, clinical neurologic examination, blood work, urine analysis, repetitive stimulation, electromyography, and muscle biopsy. A drug which induces muscular side effects should never be given again. Particularly in patients suffering from primary myopathy, myotoxic drugs should be applied with caution. The drugs which most frequently induce muscular side effects are steroids, statins, fibrates, antiretrovirals, immunosuppressants, colchicine, amiodarone, and anticancer drugs. Many drugs exhibit their myotoxic potential only in combination with other drugs or premorbid pathologic myogenic conditions.     

Psychotropic medication utilization in a child and adolescent mental health service

OBJECTIVES: This study aimed to identify rates and correlates of psychotropic drug utilization in children and adolescents in inpatient and outpatient settings. METHODS: A retrospective chart review examined 122 inpatient and 126 outpatient charts from a metropolitan child and youth mental health service in Brisbane, Australia. RESULTS: Inpatients received more psychotropic medication than outpatients (71% vs. 25%; p < 0.01). Patients receiving medication were older, had longer hospital admissions, and more complex presentations, including history of abuse or suicide attempts and more diagnoses (all p < 0.01). Selective serotonin reuptake inhibitors (SSRIs) were the most frequently used drug class (44% inpatients; 14% outpatients), primarily indicated for mood disorders (31%). SSRIs and newer antidepressants (ADs) were used more frequently in patients with a high suicide risk (p < 0.01). Atypical antipsychotics (APs) were also used (inpatients 23%; outpatients 3%), primarily for behavioral disturbances. Half of those receiving medication (51%) received polypharmacy (>1 concurrent drug), with up to four drugs used at one time. Rates of polypharmacy were highest among patients receiving antipsychotics. CONCLUSIONS: Use of psychotropic medication is frequent in this population. Future research should initially focus on inpatients and intensive treatment settings and examine both safety and efficacy of interventions for depression in young people, atypical antipsychotics for behavioral disturbances, and polypharmacy.     

Allergy to Carbamazepine: Parallel In Vivo and In Vitro Detection

Summary: Purpose: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. Methods: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross-reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ-10,11-epoxide (CBZ-E), 10-monohydroxy-CBZ (MHD), and 10,11-dihydroxy-CBZ (DIOL)]. Results: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross-reactivity to OCBZ was seen in -40% of CBZ-reactive patients in both PTs and LPAs. Conclusion: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.     

Antidepressant drug therapy in the elderly: enhancing safety and compliance

This review article addresses some of the complex issues surrounding antidepressant drug usage among elderly depressives. While primarily geared toward the psychiatrist in general practice, the article provides useful information for the nonpsychiatric physician who is frequently called upon to evaluate and treat affective disorders in the geriatric population. Since tricyclic antidepressants and lithium are the most commonly used psychotropic drugs in the treatment of depression, their side effects and adverse reactions are discussed specifically as these relate to the elderly. Suggestions are offered on how to improve safety and enhance compliance. Brief mention is made of the monoamine oxidase inhibitors and the second generation antidepressants. Dose ranges are recommended for use of these agents in geriatric patients. Finally, a section of the article reviews the most commonly encountered encountered drug interactions between tricyclic and a variety of other psychotropic and nonpsychotropic drugs.