Andreas Erfurth

Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide.

There is abundant evidence that the serotonin (5-HT) system is modulating mood and several behavioural traits and that disturbances in the regulation of this system can be associated with severe behavioural malfunctions, as aggressive implusive and suicidal behaviour.1 Recently a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was identified2 and the presence of one or two short alleles was associated with anxiety-related personality traits3 and several psychiatric disturbances, such as affective disorder4 or severe alcohol dependence.5 With respect to the importance of the 5-HT transporter in serotonergic transmission, we have genotyped the DNA of 58 Caucasian suicide victims (with unknown psychiatric diagnoses) and 110 healthy controls for the biallelic functional polymorphism in the 5-HTTLPR. We found a highly significant increased frequency of suicide victims being carriers of one or two short alleles (Fishers Exact Test, two sided, P = 0.0003), which suggests that a genetically altered protein function within the serotonergic pathway might be involved in suicidality, independently from the clinical diagnosis.

Intravenous valproate loading in acutely manic and depressed bipolar I patients.

Recently, valproate has emerged as a drug of primary choice for the treatment of acute mania, especially mixed mania and, partially, rapid cycling. Because of its relative safety, it can be administered in high doses as an oral loading therapy, with approximately 60% to 70% of patients showing a favorable response. Here we report on seven bipolar I patients, two of which have euphoric mania, three have a mixed manic state (including one patient with ultra-rapid cycling and one with very prominent depressed features), and two have solely depressed mood. All but one of the manic patients showed a rapid and favorable response to intravenous valproate loading, which built up sufficient blood levels that were maintained by subsequent oral treatment. Of the two patients with solely depressed mood, however, one experienced only minor benefits and the other showed no change in the depressive symptomatology. Intravenous valproate was tolerated without problems and also led to a drastic reduction in and eventual withdrawal of benzodiazepine treatment in two cases. All of the patients showed a drastic remission of mania with valproate blood levels at or only slightly above 50 microg/mL (blood drawn 12 hours after last application). It is interesting to note that one patient who was previously nonresponsive to oral valproate loading responded well to intravenous valproate. Besides the obvious efficacy and safety of this treatment regimen, these findings may also imply that a difference in pharmacokinetics with intravenous loading may result in a quick saturation of plasma-binding proteins, and hence, peak concentrations of valproate may be reached rapidly, which could contribute to the beneficial action, even in patients previously nonresponsive to oral valproate.

Lamotrigine in the Treatment of Schizoaffective Disorder

There is accumulating evidence for the efficacy of lamotrigine in the treatment of bipolar disorder, including bipolar depression, both as monotherapy and in combination with sodium valproate. We present the cases of 3 female patients admitted to our hospital with the diagnosis of schizoaffective disorder who were treated with lamotrigine. While dosages up to 200 mg/day, resulting in serum concentrations of less than 5 mg/l, were only partially effective, 400 mg/day (with serum concentrations >10 mg/l) led to considerable mood stability, with complete remission from paranoid symptoms. We suggest that lamotrigine might be helpful in the treatment of schizoaffective disorder, probably with serum concentrations of more than 5 mg/l.

New perspectives in the treatment of acute mania: A single case report

1. There is increasing evidence that standard treatment of mania with lithium or neuroleptics fails in many subtypes of mania, e.g. dysphoric mania or rapid cycling, and new strategies are needed. 2. This single case report reports on possibilities and pitfalls in alternative attempts to tackle a severe manic syndrome successfully. 3. In this patient, lamotrigine and valproate, the latter only in an i.v. formulation, led to a relief from mania. 4. It is concluded that the success of this treatment may be due to a common underlying mechanism of action of these drugs, most likely on the level of ion channel regulation, and that further experience with alternative formulations of standard treatments such as valproate i.v. should be collected.

Immunoglobulintherapie bei Gilles-de-la-Tourette-Syndrom

ZusammenfassungEs ist seit langem bekannt, daß Chorea Sydenham und Tics, wie sie im Rahmen eines Gilles-de-la-Tourette-Syndroms (GTS) auftreten, phänomenologische Ähnlichkeiten haben. Tics können sowohl als Symptome einer Chorea Sydenham auftreten als auch als Residualsymptomatik über Jahre persistieren. Untersuchungen aus den letzten Jahren zeigen, daß bei Kindern mit GTS nicht nur häufig Zeichen einer Poststreptokokkenerkrankung betehen, sondern die Symptomatik sich auch nach entsprechenden Therapien deutlich besserte. Wir behandelten einen 14jährigen Jungen, der alle diagnostischen Kriterien für ein GTS sowie eine genetische Belastung aufwies und eine deutliche Erhöhung des Antikörpertiters gegen Streptokokkenantigene zeigte, über 5 Tage mit 7S-Immunoglobulinen i.v. Hierunter zeigte sich auch im Langzeitverlauf eine deutliche Besserung der vorher ausgeprägten motorischen Tics und Vokaltics sowie von Verhaltensauffälligkeiten wie gestörter Impulskontrolle. Diese Befunde und die erfolgreiche Therapie unterstützen entsprechende Vorberichte und weisen, zumindest bei einigen Einzelfällen mit GTS, auf den pathogenetischen Mechanismus einer immunologisch getriggerten Störung des striatalen Dopaminsystems hin.SummaryIt has known for a long time that Sydenham’s chorea and tics, as seen in Gilles de la Tourette’s syndrome (GTS), are phenomenologically very similar. Tics may occur as symptoms of acute Sydenham’s chorea or persist over years as residual symptoms. Investigations of children suffering from GTS, including obsessive-compusilve symptoms, have provided signs of a poststreptococcal autoimmune process but also shown that treatment based on immunological interventions has been effective. We treated a 14-year-old boy showing all diagnostic criteria of GTS, familial susceptibility, and an increase in the antibody titer of streptococcal antigens with 7S immunoglobulins i.v. over 5 days. Response to this therapy was good regarding motor tics, vocal tics, and behavioral symptoms such as disturbed impulse control which still persisted after 9 months. These findings and the successful therapy underline reports of the literature and point to a pathogenetic mechanism of an immunologically triggered disturbance of the striatal dopaminergic system, at least in a subgroup of GTS.

Renal Impairment as a Possible Side Effect of Gabapentin

A bipolar I manic patient was treated successfully by adding gabapentin to perazine and clonazepam. Also initially tolerated well, an increase of creatinine after several weeks of GP (2000 mg) was observed which was reversible after discontinuation of GP. It is suggested that the possibility of renal dysfunction should be kept in mind with the usage of gabapentin.

Female Genital Disorder as Adverse Symptom of Lamotrigine Treatment

The new anticonvulsant, lamotrigine, is becoming an important tool in the treatment of bipolar disorder, including bipolar depression. Its efficacy in bipolar depression might be linked to its inhibition of serotonin uptake. We present the case of a female schizoaffective patient successfully treated with 400 mg of lamotrigine developing considerable genital disorder, a side effect well known from the treatment with selective serotonin reuptake inhibitors (SSRIs). We suggest that female genital disorder induced by high doses of lamotrigine is a serotoninergic side effect.

Elektrokonvulsionstherapie in der Behandlung der schweren Manie Kasuistik und Wissensstand

ZusammenfassungTrotz der Vielzahl der in jüngerer Zeit entdeckten pharmakotherapeutischen Möglichkeiten gestaltet sich die Behandlung der akuten Manie im Einzelfall oft schwierig. Unabhängig von der Auswahl des zunächst eingesetzten Medikamentes, sei es ein Neuroleptikum, Lithium, Carbamazepin oder Valproat, beträgt die Ansprechquote im Schnitt doch nur maximal 50–70%. Oft ist daher die Maniebehandlung durch eine Vielzahl monotherapeutischer und additiver Behandlungsversuche über mehrere Monate gekennzeichnet, bis sich eine hinreichende Affektstabilisierung zeigt. Anhand der hier beschriebenen Kasuistik soll daher an die Möglichkeit der Elektrokonvulsionstherapie (EKT) in der Maniebehandlung erinnert werden, die trotz der in der angelsächsischen Literatur berichteten hohen Erfolgsquote in Deutschland stark in den Hintergrund getreten ist. Wie die Kasuistik aufzeigt, kann sie gerade bei pharmakotherapeutisch nur schwer zu behandelnden und zugleich auch internistisch erkrankten Patienten einen schnellen Heilungserfolg bringen, und sollte daher auch bei dieser Patientengruppe frühzeitiger erwogen werden. Wie die Kasuistik aber auch zeigt, läßt sich, sofern die Option der Erhaltungs-EKT nicht umsetzbar ist, der Behandlungserfolg in der Regel nur durch eine überlappend einsetzende Pharmakotherapie aufrecht erhalten.SummaryDespite newly developed pharmacological possibilities, treatment of acute mania may still be a problem in single patients. Independent of the first choice of medication, i.e. neuroleptics, lithium, carbamazepine or valproate, the average response rate is only approximately 50–70%. Therefore, treating mania often implies a number of monotherapeutic and polypharmaceutic attempts for several months, until a sufficient mood stabilization has been reached.The aim of this case report is to remind that electroconvulsive therapy (ECT) is still in use for treating mania, which has been widely neglected in Germany despite its high success rate, mainly reported from Anglo-Saxon countries. As demonstrated in this report, ECT may be a useful tool for a fast antimanic response in patients which may be either refractory to standard treatment or are medically severely ill, and should, in our opinion, therefore be considered already at an earlier stage of treatment in this group. However, persistence of improvement can usually only be achieved with the overlapping start of drug treatment unless the option of maintenance ECT is given.

Mad scenes in early 19th-century opera.

Objective: It is our objective to examine the phenomenon of mad scenes in bel canto opera from a modern perspective.

Mianserin-induzierte Hypertonie 2 Wochen nach Absetzen von Tranylcypromin

ZusammenfassungMianserin gilt in der antidepressiven Behandlung von kardial vorgeschädigten Patienten im Vergleich zu anderen tri- und tetrazyklischen Antidepressiva als eher unbedenklich. Blutdrucksteigernde Wirkungen sind nicht zu erwarten. Im dargestellten Fall wurde ein 64jähriger Patient mit vorbekannter dilatativer Kardiomyopathie und Linksschenkelblock nach Vorbehandlung mit Tranylcypromin auf Mianserin umgestellt, woraufhin sich eine medikamentös nur schwer zu beeinflussende hypertone Blutdrucksteigerung (Maximum: 180/125 mmHg) entwickelte. Nach Absetzen von Mianserin kam es zu einer raschen Blutdrucknormalisierung. Die der Blutdrucksteigerung zugrundeliegenden möglichen noradrenergen und serotonergen Wirkmechanismen werden auf dem Hintergrund der Vorbehandlung mit Tranylcypromin diskutiert.SummaryAs compared to other tri- and tetracyclics, antidepressant therapy in patients suffering also from cardiac disease with mianserin is known to be relatively safe. Hypertensive effects of mianserin have not been described so far. We report a case of a 64 years old patient with a dilatative cardiomyopathy and left anterior hemiblock, who developed hypertension (maximum: 180/125 mmHg) during mianserin treatment. Previous treatment with tranylcypromine has been stopped two weeks before. After discontinuance of mianserin blood pressure rapidly came back to normal values. The possible noradrenergic and serotonergic mechanisms of this phenomenon are discussed in relation to pretreatment with tranylcypromine.