Edema related to treatment with psychotropic drugs.

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.

[Understanding and assessing the antidepressant drug-associated risk of bleeding]. / Das Blutungsrisiko unter Antidepressiva verstehen und einschätzen.

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.

Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data.

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.

[Effect of the direct healthcare professional communication on citalopram and escitalopram drug utilization for inpatient treatment of anxiety disorders]. / Effekt der Rote-Hand-Briefe zu Citalopram und Escitalopram auf Verordnungszahlen bei der stationären Behandlung von Angsterkrankungen.

BACKGROUND: In 2011, direct healthcare professional communication (DHPC) letters on citalopram and escitalopram were sent out to address the risk of QTc prolongation in the ECG. Healthcare professionals were informed about a reduction of the maximum recommended daily dose. Furthermore, a contraindication for QTc-prolonging co-medication was given. Previous studies noted that these instructions were implemented incompletely. AIM: For the first time, this study analyzed how the DHPC affected the prescription of citalopram and escitalopram in patients with anxiety disorders. METHODS: Drug utilization data from the project "Arzneimittelsicherheit in der Psychiatrie e. V." (AMSP) was used to examine whether the proportion of patients treated with a higher-than-recommended daily dose ("high dose") and the proportion of patients with QTc-prolonging co-medication would decrease post-DHPC (combined category of citalopram/escitalopram). RESULTS: Drug utilization data of n = 364 patients pre- and n = 262 patients post-DHPC were compared. The proportion of patients with high dose declined from 10.7% to 5.4% (p = 0.019). The proportion of patients with QTc-prolonging co-medication did not change significantly from pre- (54.7%) to post-DHPC (51.5%, p = 0.437). DISCUSSION: In accordance with previous studies, the proportion of high-dose patients decreased after DHPC publication while the proportion of patients with QTc-prolonging co-medication remained widely unchanged. The specific recommendation on daily dosage seems to have been better implemented than the broadly formulated contraindication of QTc-prolonging co-medication. Hence, DHPCs should be written precisely and give advice for specific clinical situations.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017.

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.

Atypical dyskinesias under treatment with antipsychotic drugs: Report from the AMSP multicenter drug safety project.

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.

Treatment of depression: Are psychotropic drugs appropriately dosed in women and in the elderly? Dosages of psychotropic drugs by sex and age in routine clinical practice.

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.

Antipsychotic drug treatment of schizophrenia in later life: Results from the European cross-sectional AMSP study.

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.

Urological adverse drug reactions of psychotropic medication in psychiatric inpatients - A drug surveillance report from German-speaking countries.

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.

[Vaccination Against COVID-19 in Patients Treated with Psychotropic Drugs]. / COVID-19-Impfung unter Psychopharmakotherapie.

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.

Psychotropic drug-induced hyponatremia: results from a drug surveillance program-an update.

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.

Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs-Influence of Smoking Behavior and Inflammation on Pharmacokinetics.

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.

A case series of serious and unexpected adverse drug reactions under treatment with cariprazine.

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.

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017.

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001-2003) with the last time period (2015-2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12-1.19), especially mirtazapine (RR 1.16; 95% CI 1.12-1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35-1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03-1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83-0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86-0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81-0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015-2017 than in 2001-2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

Time trends in pharmacological treatment of major depressive disorder: Results from the AMSP Pharmacovigilance Program from 2001-2017.

BACKGROUND: Currently available data on the prescription practice among patients with major depressive disorder (MDD) reflect the outpatient setting. This is the first study to provide information on time trends of psychotropic drug utilization in psychiatric inpatients. METHOD: Data stems from German-speaking psychiatric hospitals collected by the program "Drug Safety in Psychiatry" (Arzneimittelsicherheit in der Psychiatrie, AMSP) between 2001 and 2017. 44,418 psychiatric inpatients with MDD were included. Time trends in drug utilization were analyzed by comparing the first (2001-2003) and last time point (2015-2017) using risk ratios (RR). RESULTS: Antidepressant drugs (ADD) were the most used psychotropic drug class with utilization decreasing slightly from 2001-2003 (89.7%) to 2015-2017 (85.5%). Use of tricyclic ADDs showed the greatest decline (RR 0.35), while use of selective serotonin-noradrenaline reuptake inhibitors (RR 1.72) and "other ADDs" increased the most. Use of antipsychotic drugs (APD), especially second-generation antipsychotic drugs (RR 1.46), increased. Use of tranquilizing (RR 0.71) and hypnotic drugs (RR 0.43) both decreased. Most patients were treated with more than one psychotropic drug, most often ADD + APD, which was utilized more often in 2015-2017 (51.1%) than in 2001-2003 (45.1%; RR 1.13). Combination of two ADDs increased from 2001-2003 (24.5%) to 2015-2017 (33.0%; RR 1.35). LIMITATIONS: The cross-sectional design does not allow conclusions to be drawn about causal relationship of findings. Further, only certain clinical and sociodemographic data was available. CONCLUSION: Treatment of MDD has shown significant changes from 2001 to 2017.

Pharmacotherapy of 1,044 inpatients with posttraumatic stress disorder: current status and trends in German-speaking countries.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited approved pharmacological treatment options and high symptom burden. Therefore, real-life prescription patterns may differ from guideline recommendations, especially in psychiatric inpatient settings. The European Drug Safety Program in Psychiatry ("Arzneimittelsicherheit in der Psychiatrie", AMSP) collects inpatients' prescription rates cross-sectionally twice a year in German-speaking psychiatric hospitals. For this study, the AMSP database was screened for psychiatric inpatients with a primary diagnosis of PTSD between 2001 and 2017. N = 1,044 patients with a primary diagnosis of PTSD were identified with 89.9% taking psychotropics. The average prescription rate was 2.4 (standard deviation: 1.5) psychotropics per patient with high rates of antidepressant drugs (72.0%), antipsychotics drugs (58.4%) and tranquilizing drugs (29.3%). The presence of psychiatric comorbidities was associated with higher rates of psychotropic drug use. The most often prescribed substances were quetiapine (24.1% of all patients), lorazepam (18.1%) and mirtazapine (15.0%). The use of drugs approved for PTSD was low (sertraline 11.1%; paroxetine 3.7%). Prescription rates of second-generation antipsychotic drugs increased, while the use of tranquilizing drugs declined over the years. High prescription rates and extensive use of sedative medication suggest a symptom-driven prescription (e.g., hyperarousal, insomnia) that can only be explained to a minor extent by existing comorbidities. The observed discrepancy with existing guidelines underlines the need for effective pharmacological and psychological treatment options in psychiatric inpatient settings.

Severe drug-induced liver injury in patients under treatment with antipsychotic drugs: Data from the AMSP study.

OBJECTIVES: Drug-induced liver injury (DILI) has been associated with various antipsychotic drugs (APDs). Comparative studies between individual APDs are largely not available. METHODS: Antipsychotic drug utilisation data and reports of severe antipsychotic DILI were assessed by using data from an observational pharmacovigilance programme-Arzneimittelsicherheit in der Psychiatrie (AMSP)-during the period 1993-2016. RESULTS: Of the 333,175 patients treated with APDs, a total of 246 (0.07%) events of severe DILI were identified. Phenothiazines were associated with significantly higher rates of severe DILI (0.03%, 95% CI = 0.02-0.04) than thioxanthenes (0.01%, 95% CI = 0.00-0.02) or butyrophenones (0.01%, 95% CI = 0.00-0.01). Among individual drugs, olanzapine (0.12%, 95% CI = 0.10-0.16), perazine (0.09%, 95% CI = 0.05-0.15) and clozapine (0.09%, 95% CI = 0.10-0.12 ranked highest. In 78 cases (31.7%), combination therapies with antipsychotic and antidepressant drugs or with two or more APDs were considered responsible. Male sex and a diagnosis of mania were associated with significantly higher rates of severe DILI while older patients (≥65 years old) were significantly less often affected. CONCLUSIONS: In the present analysis of a representative psychiatric inpatient cohort, olanzapine, perazine, and clozapine were the most common individual APDs associated with severe DILI.

Severe weight gain as an adverse drug reaction of psychotropics: Data from the AMSP project between 2001 and 2016.

Severe weight gain induced by psychotropics is a known problem in psychiatry. Various drugs from different classes may lead to weight gain that may further lead to potentially life-shortening diseases, such as diabetes or cardiovascular disease. A total of 344 cases of severe weight gain (>10% of body weight) have been documented by the drug safety in psychiatry program AMSP between 2001 and 2016. Patients gained 12.7 ± 5.5 kg weight within 12±15 weeks. This equals a Body Mass Index (BMI) gain of 4.4 ± 1.9 kg/m² to a final BMI of 28.8 ± 5.5 kg/m². In addition, 142 retrospective reports documented at admission have been analyzed. Within one year these patients gained 6.4 ± 4.0 kg/m² to a final BMI of 31.9 kg/m². The weight gain was extreme in some cases. For example, 35% of the patients gained more than 20 kg. On average the patients reached overweight or even adiposity. Only 27% of the patients could loose some weight at the end of their stay. This emphasizes the relevance of this long-term problem for the patients' health. Mostly second generation antipsychotics, and therein olanzapine, as well as antidepressants and anticonvulsants have been imputed. Severe weight gain is a slow process and it is rarely documented as adverse drug reaction under real-life conditions compared to the high percentage of patients with weight gain in clinical studies. It might often remain unnoticed due to shorter stationary treatment and changing treatment settings.

Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013.

BACKGROUND: Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome. METHODS: This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients. RESULTS: A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine. CONCLUSIONS: Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.

Extrapyramidal reactions following treatment with antidepressants: Results of the AMSP multinational drug surveillance programme.

Objectives: Extrapyramidal symptoms (EPS) are a common adverse effect of antipsychotics. However, there are case reports describing EPS following treatment with antidepressants. It is not fully understood how antidepressants cause EPS, but a serotonergic input to dopaminergic pathways is a probable mechanism of action.Methods: Data from a multicenter drug-surveillance programme (AMSP, 'drug safety in psychiatry') which systemically documents severe drug reactions during psychiatric inpatient admissions, were reviewed to assess for EPS associated with antidepressant treatment. We identified 15 such cases, which were studied to detect similarities and to characterise risk factors.Results: We report on 15 patients with EPS following antidepressant-therapy between 1994 and 2016. EPS frequently occurred with selective serotonin reuptake inhibitor (SSRI) treatment alone (7/15 cases) or concomitant SSRI treatment (6/15 cases). EPS were most frequent with escitalopram-treatment (5 cases). The most common EPS was atypical dyskinesia (6/15 cases) followed by akathisia (4/15 cases). The mean age of onset for EPS was 54.93 years (SD 17.9). EPS occurred at any dosage and equally often in men and women.Conclusions: Our results highlight the possibility of EPS as an important, although uncommon, adverse effect of antidepressants. Clinicians should beware of this adverse effect and monitor early warning signs carefully.