Clozapine-associated adverse drug reactions in 38,349 psychiatric inpatients: drug surveillance data from the AMSP project between 1993 and 2016.

Clozapine is a second-generation antipsychotic drug that offers superior treatment results in patients with schizophrenia but is also associated with significant risks. This study analyzes data on pharmacotherapy with clozapine and the associated adverse drug reactions (ADRs) in an inpatient setting including 38,349 patients. Data about the use of clozapine and reports of severe ADRs within the period 1993-2016 were obtained from the multicentered observational pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP). In total, 586 severe clozapine-associated ADRs were documented (1.53% of all patients exposed). Patients aged ≥65 years had a higher risk of ADRs than patients aged <65 years (1.96 vs. 1.48%; p = 0.021). Significantly more ADRs were attributed to clozapine alone (396; 67.6% of all 586 ADRs) than to a combination with other drugs. The most frequent ADRs were grand mal seizures (0.183% of all 38,349 patients exposed), delirium (0.180%), increased liver enzymes (0.120%), and agranulocytosis (0.107%). We detected 24 cases (0.063%) of clozapine-induced extrapyramidal symptoms, of which 8 (0.021%) were attributed to clozapine alone. Five ADRs resulted in death (0.013%): 2 due to agranulocytosis (41 cases total) (mortality = 4.88%) and 3 due to paralytic (sub)ileus (16 cases) (mortality = 18.75%). The median dose of clozapine in all patients treated was 300 mg/day, in patients who developed ADRs 250 mg/day. The main risk factor for an ADR was pre-existing damage of the affected organ system. Overall, the results of this study highlight the importance of alertness-especially of frequently overlooked symptoms-and appropriate monitoring during treatment with clozapine, even at low doses.

[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.

[Clinical use of psychotropic drugs: A look at antipsychotic drugs]. / Psychopharmaka in der Praxis: Ein Blick auf Antipsychotika.

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.