Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46 of patients treated with pregabalin, followed by mirtazapine (0.8). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Middle Aged , Edema/chemically induced , Edema/epidemiology , Edema/drug therapy , Pregabalin , Psychotropic Drugs/adverse effects , Pharmacovigilance
BACKGROUND: The admission decision after presentation in the psychiatric emergency room (PER) has potentially far-reaching consequences for the patient and the community. In a short amount of time, information must be collected and evaluated for a well-founded admission decision. The present study aimed to identify risk factors associated with inpatient psychiatric admission (IPA) after previous emergency presentation to the PER. METHODS: Electronic patient records for all patients presenting in the PER of Hannover Medical School (MHH) in the year 2022 were retrospectively examined (n = 2580). Out of these, 2387 were included in this study. Two multivariate binary logistic regression analyses were performed to identify risk factors for IPA within sociodemographic, circumstantial and clinical variables. RESULTS: 1300 (54.5%) consultations resulted in IPA. The most significant sociodemographic and circumstantial risk factors for IPA were found to be suicide attempt (depending on method: OR 9.1-17.4), aggressive behavior towards people prior to presentation (OR 2.9, 95% CI 1.7-4.8), previous psychiatric treatment (OR 1.8, 95% CI 1.4-2.3) and transfer from another hospital or medical discipline of MHH as means of presentation (OR 6.3, 95% CI 3.0-13.0). Among psychopathological aspects, suicidal ideation (OR 3.8, 95% CI 2.9-4.9), suicidal intent (OR 116.0, 95% CI 15.9-844.8), disturbance of orientation (OR 3.7, 95% CI 2.5-5.3), delusions (OR 2.3, 95% CI 1.6-3.1), visual hallucinations (OR 2.9, 95% CI 1.6-5.1), hopelessness/despair (OR 2.4, 95% CI 1.7-3.2) and inhibition of drive (OR 1.6, 95% CI 1.3-2.1) were significantly associated with IPA. CONCLUSIONS: The admission decision is a complex process influenced by a multitude of sociodemographic, circumstantial and clinical factors. A deeper understanding of the decision-making process can be used to improve patient care and facilitate the evaluation process in the PER.
BACKGROUND: The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). METHODS: We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. RESULTS: We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9-5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7-28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3-8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1-5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. CONCLUSIONS: Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.
Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores 'difficulty to resist' (items 4 and 5) and 'thoughts about alcohol' (items 1, 2, and 3) have an internal consistency (Cronbach's alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck's Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution ('difficulty to resist' and 'thoughts about alcohol') underlying the PACS-G version.
Alcoholism , Craving , Humans , Female , Middle Aged , Male , Psychometrics , Alcoholism/diagnosis , Alcohol Drinking , Surveys and Questionnaires , Reproducibility of Results
Antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are the most commonly prescribed psychopharmacological drug group. Thus, a precise knowledge of the expected adverse drug reactions is indispensable. The increased risk of bleeding events is well documented, especially in patients treated with SSRIs. However, many other antidepressant drug groups have also been implicated in increasing the risk of bleeding. In the following review, the thrombocytic serotonin system and the respective targets of the different antidepressants are explained. Subsequently, the available literature on bleeding under the respective antidepressant classes or individual substances is presented, using data from meta-analyses whenever possible. In addition to the risk of bleeding in general, individual bleeding entities are also considered, such as gastrointestinal and cerebral hemorrhages. Finally, the effects of other drugs that increase the risk of bleeding (i. e., nonsteroidal anti-inflammatory drugs, platelet aggregation inhibitors and anticoagulants) in combination with antidepressant drugs are discussed. The information presented here is meant to guide practitioner's decision making regarding an appropriate antidepressant pharmacotherapy based on the patient's individual risk constellation.
Antipsychotic drugs were originally developed to treat the positive symptoms of schizophrenia (e.g., delusions, hallucinations). Nowadays, antipsychotic drugs are also commonly used in the treatment of geriatric patients, especially those suffering from dementia. When treating behavioural symptoms of dementia, the use of antipsychotic drugs should not be first choice and when they do present the best treatment option, they should not be used long-term. Patients suffering from schizophrenia, on the other hand, may require long-term treatment with antipsychotic drugs in order to avoid relapse. In the following, the use of antipsychotic drugs in the treatment of schizophrenia and behavioural symptoms in dementia according to the respective treatment guidelines will be explained. In addition, the pharmacological receptor profiles of frequently used antipsychotic drugs (e.g., risperidone, haloperidol, quetiapine, aripiprazole) are presented and the expected adverse drug reactions, such as extrapyramidal symptoms and hyperprolactinemia, are explained. Treatment options of the most common adverse drug reactions associated with antipsychotic drugs are also presented.
Antipsychotic Agents , Dementia , Drug-Related Side Effects and Adverse Reactions , Humans , Aged , Antipsychotic Agents/therapeutic use , Risperidone/therapeutic use , Psychotropic Drugs/therapeutic use
Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.
Depressive Disorder, Major , Long QT Syndrome , Humans , Aged , Citalopram/adverse effects , Escitalopram , Quetiapine Fumarate , Depressive Disorder, Major/chemically induced , Long QT Syndrome/chemically induced , Psychotropic Drugs
Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.
Antipsychotic Agents , Mental Disorders , Psychiatry , Psychotic Disorders , Anticonvulsants , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Female , Humans , Male , Mental Disorders/psychology , Middle Aged , Mirtazapine/therapeutic use , Off-Label Use , Olanzapine , Psychotic Disorders/drug therapy , Psychotropic Drugs/therapeutic use , Quetiapine Fumarate/therapeutic use , Retrospective Studies , Risperidone/therapeutic use , Valproic Acid/therapeutic use
BACKGROUND: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome segment 15q11-13. Behavioral traits such as temper outbursts, stereotypic, and ritualistic behavior, as well as an increased risk of psychosis accompany the syndrome, representing a major issue in the treatment of adults with PWS. Up to now, no treatment guideline for these conditions in PWS exist. This study aimed to retrospectively analyze the effect and adverse effects of treatment with aripiprazole for temper outbursts in 10 adults with PWS. RESULTS: Aripiprazole was prescribed for temper outbursts (n = 10). Treatment outcome was assessed using the Clinical Global Impression-Severity (CGI-S) and -Improvement Scale (CGI-I). Treatment success (CGI-I < 3) was observed in 70% of cases, with adverse effects from mild to partly serious extent in 60% of cases. The major adverse effect observed was increased daytime sleepiness. In total, 50% of the individuals were treated successfully for temper outbursts. The BMI did not change significantly in the successfully treated group after 6 months of treatment. CONCLUSIONS: Aripiprazole can be a treatment option for temper outbursts in people with PWS. Although a high rate of side effects was detected, their severity led to discontinuation in only 20% of the cases. Furthermore, the absence of weight gain makes aripiprazole interesting especially for the PWS population.
Prader-Willi Syndrome , Adult , Aripiprazole , Humans , Retrospective Studies , Treatment Outcome
The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin-norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD-patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.
Antipsychotic Agents , Depressive Disorder, Major , Antidepressive Agents/adverse effects , Antipsychotic Agents/adverse effects , Depressive Disorder, Major/drug therapy , Humans , Inpatients , Pharmacovigilance , Psychotropic Drugs/adverse effects
Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.
Depressive Disorder, Major , Electroconvulsive Therapy , Adiposity , Depressive Disorder, Major/therapy , Humans , Obesity , Pilot Projects , Treatment Outcome
BACKGROUND: Several researchers have shown higher concentration-dose ratios of psychotropic drugs in women and the elderly. Therefore, lower dosages of psychotropic drugs may be recommended in women and the elderly. This study describes sex- and age-related dosage of psychotropic drugs prescribed to patients with major depressive disorder (MDD) in routine clinical practice. METHOD: Influence of sex and age on dosages are analysed for the 10 most commonly prescribed drugs in our dataset consisting of 32,082 inpatients with MDD. Data stems from the European drug safety program "Arzneimittelsicherheit in der Psychiatrie". The observed sex and age differences in prescriptions are compared to differences described in literature on age- and gender-related pharmacokinetics. RESULTS: Among patients over 65 years, a statistically significant decrease in dosages with increasing age (between 0.65% and 2.83% for each increasing year of age) was observed, except for zopiclone. However, only slight or no influence of sex-related adjustment of dosage in prescriptions was found. CONCLUSION: Age appears to influence adjustment of dosage in most psychotropic drugs, but to a lower extent than data on age-related pharmacokinetics suggests. Although literature also suggests that lower dosages of psychotropic drugs may be appropriate for females, this study found women are usually prescribed the same dosage as men.
Depressive Disorder, Major , Aged , Depression , Depressive Disorder, Major/drug therapy , Female , Humans , Inpatients , Male , Psychotropic Drugs/adverse effects , Sex Factors
OBJECTIVES: The aim of this study was to describe atypical dyskinesias (AtypDs) occurring during treatment with antipsychotic drugs (APDs). AtypDs are dyskinesias showing either an unusual temporal relationship between onset of treatment and start of the adverse drug reaction (ADR) or an unusual presentation of clinical symptoms. METHODS: Data on the utilisation of APDs and reports of severe APD-induced AtypDs were collected using data from the observational pharmacovigilance programme - 'Arzneimittelsicherheit in der Psychiatrie (English: drug safety in psychiatry)' (AMSP) - from 1993 to 2016. RESULTS: A total of 495,615 patients were monitored, of which 333,175 were treated with APDs. Sixty-seven cases (0.020%) of severe AtypDs under treatment with APDs were registered. The diagnoses of schizophrenic disorders as well as organic mental disorders were related to significantly higher rates of AtypDs. Second-generation antipsychotic drugs (SGAs) showed slightly higher rates of AtypDs (0.024%) than high-potency (0.011%) or low-potency first-generation antipsychotic drugs (FGAs; 0.006%). In 41 cases (61.2%), two or more drugs were found to cause AtypDs. CONCLUSIONS: Our study indicates that AtypDs are rare ADRs. SGAs may have a higher risk for the occurrence of AtypDs than FGAs. Clinicians should be aware of this ADR and patients should be monitored and examined carefully.
Antipsychotic Agents , Drug-Related Side Effects and Adverse Reactions , Dyskinesias , Schizophrenia , Antipsychotic Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Dyskinesias/drug therapy , Humans , Pharmacovigilance , Schizophrenia/drug therapy
OBJECTIVES: To investigate the relationship between patient age and the selection and dosage of antipsychotic drugs (APDs) for treatment of schizophrenia. We describe age effects for multiple individual APDs, thus allowing comparisons between drugs. METHODS: Prescription data of 32,062 inpatients with schizophrenia from 2000 to 2017 were obtained from the Drug Safety Program in Psychiatry (AMSP) database. APD selection and dosage were related to patient age with sex as an influencing variable. Moreover, a systematic search of current guideline recommendations on APD treatment in patients with schizophrenia aged ≥65 years was performed. RESULTS: Eighty percentof elderly patients (≥65 years) received a second-generation APD, most commonly risperidone. The dosage of APDs increased with age until about age 40 years, then decreased slowly at first and more steeply beyond age 55 years. The influence of age as well as sex on dosage partly differed between the individual drugs. Only one of eight schizophrenia guidelines systematically addressed specific aspects of pharmacotherapy in older adults. CONCLUSIONS: In clinical routine, age has a significant impact on selection and dosing of APDs. Information on optimising pharmacotherapy in older adults with schizophrenia from clinical trials is needed. Guidelines should be improved regarding APD therapy specifically for older adults.
Antipsychotic Agents , Schizophrenia , Aged , Female , Humans , Male , Antipsychotic Agents/adverse effects , Cross-Sectional Studies , Psychiatry , Risperidone/adverse effects , Schizophrenia/drug therapy
Urological adverse drug reactions (UADR) are common during treatment with psychotropic medication. The aim of this study was to provide a systematic description of the differential profile of UADR of psychotropic drugs in a large naturalistic population. Data stems from psychiatric hospitals collected by AMSP (Arzneimittelsicherheit in der Psychiatrie), a continuous multi-center pharmacovigilance program in Austria, Germany, and Switzerland. 171 cases of severe UADR (0.037%) among a total population of 462 661 inpatients treated with psychotropic drugs in 99 psychiatric hospitals between 1993 and 2016 were examined. Urinary retention (129 cases, 0.028%) was the most common UADR followed by incontinence (23 cases, 0.005%) and nocturnal enuresis (16 cases, 0.003%). Risk of UADR was higher in patients with mania than in other diagnostic groups. Promethazine and haloperidol were the antipsychotics with the highest rate of UADR. Tricyclic antidepressants had a higher and selective serotonin reuptake inhibitors a lower risk for UADR than the respective other antidepressants. Amitriptyline and clomipramine were the most common causes of urinary retention and clozapine of urinary incontinence. This research improves our knowledge of the urological risk profiles of psychotropic drugs in inpatients and highlights compounds associated with higher or lower risk.
Antipsychotic Agents , Drug-Related Side Effects and Adverse Reactions , Pharmaceutical Preparations , Antipsychotic Agents/therapeutic use , Drug-Related Side Effects and Adverse Reactions/drug therapy , Humans , Inpatients , Pharmacovigilance , Psychotropic Drugs/adverse effects
Vaccines against SARS-CoV-2 have been available in the European Union since December 2020. Persons suffering from mental illness have an increased risk of a severe or fatal course following an infection with SARS-CoV-2. Thus, the question arises to what extent interactions between the newly approved vaccines and psychotropic drugs may be expected. Data on the tolerability and efficacy of vaccines against SARS-CoV-2 under treatment with psychotropic drugs are not available to date - however, potential interactions can be derived from previous investigations on vaccines against other pathogens, such as a reduced immune response with lower clinical efficacy and an increase in drug plasma levels due to the indirect vaccine-mediated inhibition of metabolizing enzymes. On the other hand, depressed patients treated with antidepressant medication show a better immune response.
COVID-19 , COVID-19 Vaccines , Germany , Humans , Psychotropic Drugs/adverse effects , SARS-CoV-2 , Vaccination
Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of < 130 mmol/l) and often induced by drugs including psychotropic drugs. AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicenter drug surveillance program that assesses severe or unusual adverse drug reactions (ADRs) occurring during treatment with psychotropic drugs. This study presents data from 462,661 psychiatric inpatients treated in participating hospitals between 1993 and 2016 and serves as an update of a previous contribution by Letmaier et al. (JAMA 15(6):739-748, 2012). A total of 210 cases of HN were observed affecting 0.05% of patients. 57.1% of cases presented symptomatically; 19.0% presented with severe symptoms (e.g., seizures, vomiting). HN occurred after a median of 7 days following the first dose or dose increase. Incidence of HN was highest among the two antiepileptic drugs oxcarbazepine (1.661% of patients treated) and carbamazepine (0.169%), followed by selective serotonin-norepinephrine reuptake inhibitors (SSNRIs, 0.088%) and selective serotonin reuptake inhibitors (0.071%). Antipsychotic drugs, tricyclic antidepressants, and mirtazapine exhibited a significantly lower incidence of HN. The risk of HN was 16-42 times higher among patients concomitantly treated with other potentially HN-inducing drugs such as diuretic drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and proton pump inhibitors. Female SSNRI-users aged ≥ 65 years concomitantly using other HN-inducing drugs were the population subgroup with the highest risk of developing HN. The identification of high-risk drug combinations and vulnerable patient subgroups represents a significant step in the improvement of drug safety and facilitates the implementation of precautionary measures.
Hyponatremia , Pharmaceutical Preparations , Adverse Drug Reaction Reporting Systems , Aged , Antidepressive Agents , Female , Humans , Hyponatremia/chemically induced , Hyponatremia/epidemiology , Psychotropic Drugs/adverse effects
INTRODUCTION: The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). METHODS: Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. RESULTS: The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%-25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%-22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41-1.70, severe depression 1.33, 95% CI 1.18-1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27-1.38, PIM 1.18, 95% CI: 1.14-1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11-1.46, PIM 1.27, 95% CI: 1.11-1.44), respectively. CONCLUSION: This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.
Antidepressive Agents/therapeutic use , Depression/drug therapy , Drug Interactions , Potentially Inappropriate Medication List , Antipsychotic Agents/therapeutic use , Drug Therapy, Combination , Humans , Logistic Models , Middle Aged , Probability , Risk Factors
Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring ("black triangle" label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.
Both inflammation and smoking can influence a drug's pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients' drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior-both clinically relevant in psychiatry-that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment.
