D. Schreinzer

Suicide by antidepressant intoxication identified at autopsy in Vienna from 1991-1997: the favourable consequences of the increasing use of SSRIs

In the area of Vienna, any person dying under questionable circumstances is examined at the Institute of Forensic Medicine, where the cause of death is determined by means of autopsy and chemical analysis. Our study on fatal intoxications was performed in the period between 1991 and 1997, when selective serotonin reuptake inhibitors (SSRIs) were establishing themselves on the market, reaching the top of prescription statistics. Tricyclic antidepressants (TCAs) were involved in 30 single- and 127 multiple-substance intoxications, with amitriptyline and doxepin being the most frequently used drugs. SSRIs were involved in five multiple-substance intoxications. The f-value, which refers to the number of deaths per million defined daily doses prescribed, was found to be significantly (P</=0.001) higher in TCAs than in SSRIs. The f-value for the total group of all antidepressants declined significantly (P</=0.05) during the observation period of 7 years. In conclusion, SSRIs turned out to be less toxic than TCAs, and the increasing use of new antidepressants did not coincide with an increased number of deaths caused by these drugs.

Einsatz der Elektrokrampftherapie in der Psychiatrie

ZusammenfassungDie Elektrokrampftherapie (Elektrokonvulsionstherapie, EKT) hat antidepressive und antipsychotische Wirkungen. Seit den ersten Behandlungen (Italien, 1938) ist der Wirkmechanismus ungeklärt geblieben. Die Durchführung wurde in vielerlei Hinsicht modifiziert. Die EKT, bei der durch elektrische Stimulation des Gehirns ein generalisierter epileptischer Anfall ausgelöst wird, erfolgt unter intravenöser Kurznarkose und Muskelrelaxation. Nach sorgfältigen Voruntersuchungen und der Berücksichtigung anästhesiologischer oder internistischer Gegenanzeigen gilt die EKT als sehr sichere Behandlungsform. Persistierende Gedächtnisdefizite wurden nach der früher üblichen bilateralen Applikation von Sinuswellenstrom kasuistisch beschrieben. Durch die Verwendung von Kurzimpulsstrom, die unilaterale Elektrodenplatzierung und die individuelle Dosierung der Ladung (Voraussetzung: EEG-Monitoring) treten Gedächtnisstörungen nach EKT heutzutage seltener auf, und sie remittieren meist komplett innerhalb von 4 bis 8 Wochen. Zur Zeit kommt die EKT insbesondere bei PatientInnen mit therapieresistenten, schwergradigen affektiven oder schizophrenen Störungen zum Einsatz. Die perniziöse Katatonie und das maligne neuroleptische Syndrom stellen eine Notfallindikation dar. Für eine suffiziente EKT ist eine Serie von 6 bis 12 Einzelbehandlungen (jeden 2.–3. Tag) notwendig. Die Responserate bei therapieresistenten Depressionen – zu dieser Indikation gibt es die meisten Daten – ist 50 bis 60%. Dies wird durch eine deskriptive Auswertung aller EKT-Behandlungen an der Psychiatrischen Abteilung der Universitätsklinik Wien, 1994 bis 2000, bestätigt. Ein Bedarf besteht an kontrollierten Studien zur Erhaltungstherapie nach EKT-Serien.SummaryElectroconvulsive therapy (ECT) has antidepressive and antipsychotic effects. Since being introduced in Italy in 1938, its mode of action has still not been clarified. Treatment modalities have changed in many ways. ECT, in which a generalized epileptic seizure is provoked by electrical stimulation of the brain, is performed under short intravenous anesthesia and muscle relaxation. Considering careful previous clinical examination and anesthesiological and internal counterindications, ECT is a very safe form of treatment. Single cases of persisting memory impairment were described after the formerly common bilateral sinus wave stimulation. However, recent developments such as brief pulse stimulation, unilateral electrode placement, and individual stimulus titration (on the basis of EEG monitoring) make memory impairment as a consequence of ECT a rare event which mostly remits completely in 4–8 weeks. Today, ECT is performed mainly in patients suffering from severe, therapy-resistant affective or schizophrenic disorders. Pernicious catatonia and the neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment requires a series of 6–12 individual sessions (every second or third day). In therapy-resistant depression, for which the greatest number of data are available, the response rate lies between 50 and 60%. This has been confirmed by a descriptive analysis of all ECT treatments at the Department of Psychiatry, University of Vienna, between 1994 and 2000. There is a need for controlled studies on continuation therapy subsequent to successful ECT.

Inverse Relation Between Stimulus Intensity and Seizure Duration: Implications for Ect Procedure

A retrospective analysis of the effects of electroconvulsive therapy (ECT) was performed for two groups of 11 patients matched according to age (mean age, 52 years), sex, and diagnosis. Group 1 received ECT according to the age–dose protocol; group 2 was treated according to the titration method. A higher dose relative to the seizure threshold appeared to shorten the seizure duration. At the first treatment, the correlation between stimulus intensity and seizure duration was negative. In the titration group, the initial mean charge of 91 mC resulted in a seizure duration of 51 s, whereas in the age–dose group the seizure duration of 31 s was significantly shorter despite a higher mean charge of 312 mC. Seizure duration decreased during the ECT course in the group treated first at low dose (titrated) and then at 2.5 times the initial threshold. High stimulus intensity represented adequate treatment, although it produced short seizures. Thus, seizure duration proved to be an unreliable guideline for effective treatment. Furthermore, focus on seizure duration led to frequent high-dose restimulation in the elderly. The titration method obviates inadequate or excessive charges because the seizure threshold must first be determined.

Different fatal toxicity of neuroleptics identified by autopsy

Autopsies and toxicological analyses at the Institute of Forensic Medicine revealed 85 fatal intoxications with neuroleptics in Vienna from 1991 to 1997. A total of 17 cases were linked to a single neuroleptic (NL) alone, while 68 deaths were attributed to a combination of NLs with other drugs. The most frequently detected agent was prothipendyl (n=41). During the study period the number of defined daily doses of high-potency NLs prescribed increased significantly (P< or =0.001) due to increased prescribing of new atypical antipsychotics. The quantity of intermediate- and low-potency NLs dispensed remained stable. The most frequently prescribed NL was haloperidol. The relative toxicities of different NLs were calculated by dividing the number of deaths caused by this NL into the number of defined daily doses prescribed in the observation period (f-value). Single-substance intoxications and multiple-substance intoxications were distinguished. The highest f-values were associated with low-potency NLs, especially with prothipendyl, chlorprothixene and levomepromazine. Low f-values were found for the group of high-potency NLs, including flupentixol, fluphenazine, haloperidol and pimozide, as well as olanzapine. Compared to the f-values for all NLs prescribed, f-values for low-potency NLs were shown to be significantly higher concerning single-substance intoxications (P< or = 0.05) and multiple-substance intoxications (P < or = 0.001), while f-values for high-potency NLs were significantly lower (P< or = 0.05 and P< or = 0.001). We are not aware of the psychiatric diagnoses in our post-mortem sample. However, the present results indicate that careless use of low-potent NLs should be avoided in patients with a potential risk of accidental or suicidal overdose.

Letale Intoxikationen mit Antidepressiva und NeuroleptikaAnalyse im Zusammenhang mit den Verordnungen in Wien von 1991 bis 1997

ZusammenfassungWegen des zunehmenden Einsatzes der selektiven Serotoninwiederaufnahmehemmer (SSRI) verdoppelte sich die Zahl der verordneten Antidepressiva (AD) in Wien zwischen 1991 und 1997. Gleichzeitig wurden am Institut für Gerichtliche Medizin der Universität Wien 164 fatale Intoxikationen mit AD durch Autopsien und chemische Analysen nachgewiesen. Die von uns berechneten fatalen Toxizitätsindizes (f-Indizes) sagen aus, wie viele letale Intoxikationen es pro einer Million verordneter, definierter Tagesdosen gab. Der f-Index für Mono- und Polyintoxikationen war bei SSRI signifikant (p<0,001) niedriger als bei trizyklischen AD (TCA). Monointoxikationen (n=30) fanden sich überhaupt nur mit TCA. Der Zuwachs an Neuroleptika (NL)-Verordnungen war im Beobachtungszeitraum nicht so deutlich ausgeprägt (plus 30%). Gleichzeitig wurden 85 letale Intoxikationen mit NL nachgewiesen. Auch bei den NL wiesen die Trizyklika (TCNL) einen signifikant (p<0,001) höheren f-Index auf als andere NL-Gruppen. Von den 17 Monointoxikationen ereigneten sich 14 unter TCNL, keine unter Butyrophenonen bzw. Haloperidol. Unsere Daten zeigen auf, dass der Einsatz trizyklischer AD oder NL im Hinblick auf mögliche letale Intoxikationen mit einem relativ großen Risiko verbunden ist.SummaryAs a result of the increasing use of selective serotonin reuptake inhibitors (SSRI), the number of antidepressants (AD) prescribed in Vienna doubled from 1991 to 1997. In the same period, autopsies and chemical analyses performed at the Institute of Forensic Medicine, University of Vienna, revealed a total of 164 fatal intoxications by means of AD. In this study, the number of fatal intoxications per million defined daily doses prescribed was determined and referred to as the fatal toxicity index (f-index). For both single- and multiple-substance intoxications, it proved to be significantly (p<0.001) lower with SSRI than with tricyclic antidepressants (TCA). Single-substance intoxications (n=30) were seen exclusively in TCA. Concerning neuroleptics (NL), the increase in prescriptions observed in the study period (plus 30%) was less pronounced, and they were found to be involved in 85 fatal intoxications. Also in NL, those of the tricyclic type (TCNL) showed a significantly (p<0.001) higher f-index than other groups. Out of a total of 17 single-substance intoxications, 14 were caused by TCNL and none by butyrophenones or haloperidol. The present study demonstrates that the prescription of TCA or TCNL involves a relatively high risk of fatal intoxication.

Topiramate as a mood stabilizer.

Topiramate is a novel anticonvulsant agent with a broad spectrum mechanism of action, and recent clinical reports indicate that it may have mood stabilizing properties in bipolar disorder. Therefore, we treated a 41-year-old woman who had 12 previous hospitalizations for acute mania during a 10-year history of bipolar I disorder with this compound. Since 1991, the patient had been treated with carbamazepine, valproate and lamotrigine with limited success. At the beginning of a new manic episode, topiramate was started in the outpatient clinic. Eight weeks after initiation of treatment, the patient was hospitalized. This inpatient treatment lasted less than 3 weeks. Subsequently, the patient has not been hospitalized again. Topiramate was well tolerated. Even though, during subsequent topiramate treatment, a serious life event (suicide attempt of brother) induced re-occurence of the patients psychopathology, which did not require hospitalization. Fortunately, inpatient treatment was not necessary due to an increase of topiramate dosage and addition of risperidone and clonazepam. The patient, now on 200 mg/day, is mostly asymptomatic and has functioned well for over 17 months, in contrast to 13 hospitalizations during the previous 10 years.

Typical neuroleptics vs. atypical antipsychotics in the treatment of acute mania in a natural setting.

The present retrospective chart review documents the treatment practice of in-patients suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, Medical University of Vienna between 1997 and 2001. The aim of the study was to compare the efficacy of typical neuroleptics and atypical antipsychotics as add-on therapy to mood stabilizers. A total of 119 episodes of consecutively admitted patients with ICD-10-defined acute mania (n=106) or hypomania (n=13) were included in a retrospective analysis. Two subgroups were separated out of the whole patient sample according to the medication used: (a) mood stabilizer+typical neuroleptic (n=27) and (b) mood stabilizer+atypical antipsychotic (n=39). The treatment patterns of both subgroups during the first 14 d of in-patient treatment were evaluated. The therapeutic effect was measured by the Clinical Global Impression Scale (CGI). Both patient groups showed no differences on CGI at admission. Patients treated with atypical antipsychotics showed a significantly greater clinical improvement after 14 d (p<0.005) and on discharge (p<0.05) than patients treated with typical neuroleptics. Furthermore, patients treated with atypical antipsychotics developed significantly less extrapyramidal side-effects (p<0.01) and were significantly treated less often with benzodiazepines (p<0.05) during the first 14 d compared to the group receiving typical neuroleptics. Based on our evaluation and the data available in the literature atypical antipsychotics can be considered as first choice for the treatment of acute mania as add-on therapy to mood stabilizers because of their better efficacy and side-effect profile compared to typical neuroleptics.