Markus Wittmann

QTc Prolongation by Psychotropic Drugs and the Risk of Torsade de Pointes

INTRODUCTION Many psychotropic drugs can delay cardiac repolarization and thereby prolong the rate-corrected QT interval (QTc). A prolonged QTc often arouses concern in clinical practice, as it can be followed, in rare cases, by the life-threatening polymorphic ventricular tachyarrhythmia called torsade de pointes (TdP). METHOD We searched PubMed for pertinent literature on the risk of QTc prolongation and/or TdP associated with commonly used psychotropic drugs. RESULTS Thioridazine and ziprasidone confer the highest risk of QTc prolongation and/or TdP. There is also a clinically significant risk associated with haloperidol given intravenously in high doses. TdP has been reported in a few cases in association with the use of newer antipsychotic drugs (mainly quetiapine and amisulpride), most of the tri- and tetracyclic antidepressants, and the selective monoamine reuptake inhibitors citalopram, fluoxetine, paroxetine, and venlafaxine. As a rule, however, QTc prolongation and/or TdP occur only in the presence of multiple additional risk factors, such as age over 65 years, pre-existing cardiovascular disease, bradycardia, female sex, hypokalemia, hypomagnesemia, a supratherapeutic or toxic serum concentration, or the simultaneous administration of other drugs that delay repolarization or interfere with drug metabolism. CONCLUSION Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The ECG and electrolytes should be regularly monitored in patients taking psychotropic drugs.

Hypothermia Associated With Antipsychotic Drug Use: A Clinical Case Series and Review of Current Literature

Hypothermia as an adverse reaction of antipsychotic drug use represents a potentially life‐threatening complication. However, the mechanisms by which antipsychotic drugs alter thermoregulatory processes in the human body are far from being fully understood. Here we present a case series of 5 patients developing severe hypothermia after administration of olanzapine and benperidol. Controlled by a network of neural structures, body temperature is physiologically regulated in far more narrow boundaries than are other vital functions, and its homeostasis is critical for survival. The preoptic region in the ventral hypothalamus is assumed to act as a coordinating center that is endowed with thermosensory units that constantly compare actual body temperature with target values and initiate regulatory and compensatory mechanisms in case of mismatch. Hypothermia risk seems to increase in the first days after initiation of antipsychotic drug therapy or increases in the daily dose. Schizophrenic patients bear a higher risk than nonschizophrenic patients treated with antipsychotic drugs (such as patients with dementia or depression). Antipsychotic drugs with strong 5‐HT2 antagonism seem to be more frequently associated with hypothermia. These cases demonstrate the clinical relevance of hypothermia as an adverse reaction to antipsychotic treatment and the importance of careful monitoring of body temperature.

Patterns of referring of patients with frontotemporal lobar degeneration to psychiatric in- and out-patient services: Results from a prospective multicentre study

Dementia with frontotemporal lobar degeneration (FTLD) is clinically characterized by the occurrence of various psychiatric symptoms. In a recent study, the hospital-based prevalence of FTLD and the circumstances of the patients’ admission to German psychiatric state hospitals were estimated. On the basis of further continuous assessment, this original FTLD group (n = 33) has been enlarged to 58 patients. The authors here present demographic and clinical data, and reasons for admission to geriatric psychiatry hospitals in comparison with 17 patients, who primarily attended the Memory Disorders Clinic of the University of Regensburg. The results implicate that both institutions see patients with different clinical syndromes: (1) patients were primarily referred to the Memory Disorders Clinic presenting memory and/or speech difficulties as the leading symptoms; (2) major reasons for hospitalisation of patients with FTLD in geriatric psychiatry hospitals were behavioural disturbances; (3) late-onset FTLD (>65 years) was more common than previously assumed in both institutions, and (4) increasing age at admission increased the likelihood to obtain a limited diagnostic approach of brain imaging (only cranial computer tomography) to evaluate the cause of dementia.

Completed Suicides in 47 Psychiatric Hospitals in Germany - Results from the AGATE-Study

INTRODUCTION There is an ongoing debate about a possibly enhanced risk of suicidal behaviour in some psychiatric patients due to psychopharmacotherapy. Our retrospective study aimed at analyzing the psychopharmacotherapy of 133 inpatient suicides and 133 controls by a matched pair design. METHODS We analyzed all suicides (n = 133) reported in the AGATE study from 1991 to 2008. Besides evaluation of sociodemographic variables and suicide methods, we compared psychopharmacotherapy of suicides with schizophrenia (n = 59) and affective disorders (n = 59) to that of a matched control group. RESULTS Most suicides (n = 102, 76.7%) were judged not to be related to psychopharmacotherapy. In general, more psychopharmacological drugs were prescribed for suicides than for controls. Schizophrenic suicides received more low potency FGAs than their controls. More suicides with affective disorders than controls were treated with NASSAs, SNRIs, and high or low potency FGAs. In contrast to their controls, none of the suicides with affective disorders received lithium. NASSAs, SNRIs, and high or low potency FGAs predicted suicide in regression analysis for inpatients with affective disorders. DISCUSSION Differences in psychopharmacotherapy might mainly result from a recognized risk of suicide or a more severe degree of illness. However, the underrepresentation of lithium in the suicide groups is noticeable.

Acute psychiatric inpatient care: a cross-cultural comparison between two hospitals in Germany and Japan.

Background: Intercultural differences influence acute inpatient psychiatric care systems. Aims: To evaluate characteristics of acute inpatient care in a German and a Japanese hospital. Method: Based on a sample of 465 admissions to the Psychiatric State Hospital Regensburg (BKR) and 91 admissions to the Hirakawa Hospital (HH) over a six-month period in 2008, data from the psychiatric basic documentation system (BADO) were analysed with regard to socio-demographic characteristics, treatment processes and outcome indicators. Results: Schizophrenia and related psychosis was the most common diagnosis in both hospitals. Cases at the BKR were admitted more quickly after onset of the present episode. Global Assessment of Psychosocial Functioning (GAF) ratings at admission were lower at the HH. Most admissions to both hospitals received psychopharmacological treatment, but more at the HH received psychotherapy. Length of stay was significantly longer at the HH (75 days) than at the BKR (28 days). Admissions to the HH were more improved with regard to GAF and clinical global impression (CGI). Conclusions: Acute admissions in Germany provide intensive care with short hospitalization as crisis intervention. For acute admissions in Japan, comprehensive care for severe mental illness precedes emergency admissions and achieves greater improvement with longer hospitalization.

Folgen neu erkannter Arzneimittelrisiken auf die Antipsychotikaverordnung bei Demenzerkrankten

OBJECTIVE We investigated the change of antipsychotic treatment of elderly persons with dementia after several publications indicated an association between use of antipsychotics and cerebrovascular events in this population. METHODS Twice a year, the complete medication, age, diagnosis and gender of all inpatients in 30 German psychiatric sites is collected anonymously in a data base for statistical analysis. RESULTS The treatment changed for the benefit of Quetiapine and Haloperidol. The use of both Risperidone and Olanzapine decreased markedly. CONCLUSION The antipsychotic treatment changed due to critical publication. But, the evidence for the risk profile is still a matter of debate.

Persistent tinnitus induced by tricyclic antidepressants

We read with interest the report by Mendis and Johnston ‘An unusual case of prolonged tinnitus following low-dose amitriptyline’ (Mendis and Johnston, 2008). The authors describe the induction of persisting tinnitus after 3 days’ intake of 10mg amitriptyline and propose amitriptylineinduced ototoxicity with increase of glutamatergic transmission in the peripheral auditory system as a potential explanation. We would like to comment on several aspects of this report, present a similar case and discuss the relationship between tinnitus and tricyclic antidepressants. Tinnitus is a frequent symptom: the yearly incidence is estimated to be about 1% (Hoffman and Reed, 2009). Thus caution concerning causal attributions is warranted when onset of tinnitus occurs in conjunction with specific drug therapy. This is even more important when the relationship between tinnitus and antidepressants is investigated, since tinnitus and depression frequently occur together (Langguth et al., 2007). It is assumed that phantom perceptions such as tinnitus arise when primary or secondary sensory cortex areas become overactive. Such an overactivation is due to changes in the balance between inhibitory and facilitatory mechanisms, which, in turn, result either from lack of sensory input (bottom-up) or alteration of higher functions, such as attentional processes (top-down). Accordingly, in drug-induced tinnitus either an effect of the specific drug on the auditory periphery or on central top-down processes has to be assumed. Thus drugs that induce hearing loss, such as salicylate, aminoglycosides, quinine or cisplatin, are also known to induce tinnitus. However, it is important to state that this form of drug-induced tinnitus is always associated with disturbed hearing function. An alternative mechanism for the induction of drug-induced tinnitus may be the modulation of neural processing in the central nervous system. Interestingly, such an effect has recently been demonstrated for salicylate (Sun et al., 2009). Case

Verwirrtheitszustände als wichtige Arzneimittelwirkung

Delirium may be induced by a variety of reasons, among them drugs and in particular the combination of drugs. In elderly people a delirium is often misinterpreted as dementia. Anticholinergic activity is the mode of action by which drugs cause delirium. Antipsychotic drugs, antidepressants, antihistamines, and of course anticholinergic drugs themselves are the major anticholinergic classes of drugs. In addition some opioids have anticholinergic effects. Other drugs may induce delirium by dehydration (loop diuretics like furosemide) or sedation (benzodiazapines like lorazepam). Elderly people are at especially high risk to develop delirium, because of the multitude of drugs often prescribed to them, because they tend to drink to little, and because their brain is more sensitive to psychoactive drugs.

Störung zirkadianer Rhythmen im Kontext depressiver Erkrankungen

Depressive disorders are associated with various neurobiological alterations like hyperactivity of the hypothalamic-pituitary-adrenal axis, altered neuroplasticity and altered circadian rhythms. Relating to the circadian symptoms, a process is adopted in which individual genetic factors together with social, psychological and physical stressors may lead to a decompensation of the circadian system. The causal connections between depressive disorders and disturbed circadian rhythms have not been completely clarified. Chronobiological therapy is based on these disturbed processes. For the treatment of the circadian symptoms, various scientifically tested chronotherapeutics are available with however different effectiveness and evidence like light therapy or sleep deprivation. The successful treatment of depression also frequently leads to a improvement in altered circadian rhythm.

Gefährliche Kälte durch Neuroleptika: Hypothermie

Veränderungen der Körpertemperatur nach Gabe antipsychotisch wirksamer Substanzen werden im klinischen Alltag seit jeher beobachtet. Während Fieber als unerwünschte Arzneimittelwirkung (UAW)wohlbekannt ist, finden gegenläufige Störungen der Thermoregulation im Sinne einer Erniedrigung der Körpertemperatur weitaus geringere Beachtung. Dabei ist die Antipsychotika-assoziierte Hypothermie eine klinisch hochrelevante, potenziell lebensbedrohliche UAW und könnte bei vielen ungeklärten klinischen Verschlechterungen bei psychiatrischen Patienten eine Rolle spielen.