Martin Letmaier

No association of clock gene T3111C polymorphism and affective disorders

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme

Hyponatraemia (HN) can be a life-threatening medical condition which may lead to severe neurological and psychiatric symptoms. The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicentre drug surveillance programme that assesses severe or new adverse drug reactions during psychopharmacological treatment in psychiatric inpatients. We report on a total of 263 864 psychiatric inpatients monitored from 1993 to 2007 in 80 psychiatric hospitals in Germany, Switzerland and Austria. During this period plasma sodium levels below 130 mmol/l (severe HN according to AMSP) were reported in 93 patients (relative frequency 0.04%). On average, the plasma sodium levels of all cases were 119.7 mmol/l (±5.8 s.d.); median 121 mmol/l (range 104-129 mmol/l). Patients who showed no clinical signs (n=65, 70%) had a mean sodium level of 121.3 mmol/l (±5.0 s.d.); median 122 mmol/l (range 114-129 mmol/l). By contrast, patients with clinical symptoms (n=28, 30%) had a mean sodium level of 116.0 mmol/l (±6.0 s.d.); median 117 mmol/l (range 104-125 mmol/l). HN was mainly observed during treatment with selective serotonin reuptake inhibitors (SSRIs) (0.06%), Serotonin noradrenaline reuptake inhibitors (SNRIs) (0.08%), carbamazepine (0.10%) and oxcarbazepine (1.29%); the highest rate was found for oxcarbazepine. Antipsychotics, mirtazapine and tricyclic antidepressants were only rarely involved in HN (0.003-0.005%). Combinations of several drugs known to induce HN significantly increased the risk of HN, e.g. more than 10-fold for SSRI+diuretics+ACE inhibitors (0.37%) vs. SSRI given alone (0.02%). This is clinically relevant because such combinations, e.g. SSRI+diuretics may occur especially in elderly patients, who are in general at higher risk of developing HN.

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.

Impaired Ideomotor Limb Apraxia in Cortical and Subcortical Dementia: A Comparison of Alzheimer’s and Huntington’s Disease

Background: Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer’s disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington’s disease (HD). Methods: To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. Results: There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands’ imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers’ imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. Conclusions: Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful.

Venous thromboembolism during treatment with antipsychotics - results of a drug surveillance program.

Abstract Objectives: Venous thromboembolism (VTE) can be a life-threatening medical condition that may lead to leg swelling, respiratory distress and death. Methods: The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a continuous multicentre drug surveillance programme that assesses severe adverse drug reactions during treatment of psychiatric inpatients. We report on a total of 264,422 inpatients who were treated with antipsychotics (APs) and monitored from 1993 to 2011 in 99 psychiatric hospitals. Results: During this period VTE events were reported for 89 inpatients, corresponding to an occurrence rate of 34 cases per 100,000 inpatient admissions treated with APs or 43 cases per 10,000 person-years. The occurrence of VTE was greatest in patients over the age of 65 years of age with mood disorders. The chemical class of butyrophenones (48/100,000) followed by atypical APs (36/100,000) showed the highest occurrence rate for VTE compared to thioxanthenes (23/100,000), which were less associated with VTE. If imputed alone, pipamperone (61/100,000) and risperidone (55/100,000) were most frequently associated with VTE. In general, there was no difference in occurrence rate of VTE between high- and low-potency APs. Conclusions: These results suggest that clinicians should consider AP drug exposure as a potential risk factor for VTE for patients older than 65 years. Additionally, the diagnosis of an affective disorder seems to increase the risk for VTE.

Brain electrical source imaging in manic and depressive episodes of bipolar disorder

Bipolar disorder (BD) electroencephalographic (EEG) studies have reported varying results. The present study compared EEG in BD during manic and depressive episodes, using brain electrical source imaging [standardized low‐resolution electromagnetic tomography (sLORETA)] to assess the cortical spatial distribution of the sources of EEG oscillation frequencies.

Severe psychotic exacerbation during combined treatment with aripiprazole/haloperidol after prior treatment with risperidone.

Abstract Objective. Aripiprazole is a new generation antipsychotic drug that shows a partial agonistic activity at D2 and 5-HT1A receptors. This might lead in some cases to an exacerbation of psychotic symptoms due to dopamine agonism. Methods. We report the case of a 39-year-old woman with an ICD-10 defined schizoaffective disorder. Results. Risperidone was started to treat psychotic symptoms. Psychotic symptoms disappeared but because of galactorrhoea risperidone needed to be discontinued. Subsequently, an antipsychotic treatment regimen with aripiprazole and haloperidol was prescribed. After initiating aripiprazole and haloperidol the patients psychotic symptoms increased drastically. Therefore aripiprazole and haloperidol were discontinued. Olanzapine was prescribed and psychotic symptoms declined again. Conclusion. Concurrent causes for this serious adverse event may be the partial agonistic activity of aripiprazole at D2 receptors as well as an up-regulation of dopamine receptors during prior treatment with risperidone. Both aspects may have contributed to the severe psychotic exacerbation. Clinicians should be aware of this possible, serious adverse event while switching to aripiprazole or prescribing aripiprazole with other antipsychotics. Because of their lower D2 receptor affinity quetiapine and clozapine might be a better choice for combined treatment with aripiprazole.

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.