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Purpose: In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment. Methods: SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany. Results: According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds. Conclusion: This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation. [ABSTRACT FROM AUTHOR]

Psychotropic drugs may induce impairments in the mouth, jaw and face area. Currently, appropriate pharmacoepidemiologic data are missing. Therefore, a questionnaire-based telephone survey of two non-representative samples of psychiatrists and dentists was conducted. Most of the psychiatrists (79.7%) and dentists (76.5%) indicated that psychotropic drugs may induce dental adverse drug reactions (ADR); in both samples there was an approximately equally sized, relevant proportion of participants who did not believe in the risk of dental ADR of psychotropic drugs (psychiatrists 20.3%; dentists 23.5%). About one third of the participants of both samples (psychiatrists 34.9%; dentists 35.9%) felt that dental ADRs of psychotropic drugs are a serious health problem. The majority of both groups (psychiatrists 97.8%; dentists 97.0%) had never reported a dental ADR. Most psychiatrists and dentists appeared to be aware of the risk of dental ADRs by psychotropic drugs. A relevant proportion of participants of both groups considered psychotropic drugs to be irrelevant regarding dental ADRs; therefore, there may be information needs in both groups. The willingness to report dental ADRs of psychotropic drugs was low in both groups; the evaluation of the actual relevance of this drug-related risk is impeded by the absence of reports of suspected ADRs. [ABSTRACT FROM AUTHOR]

Pharmacological neuroenhancement (PNE) is a form of abuse and has not yet been addressed by methods of pharmacovigilance. In the present study, we tested if quantitative signal detection may be sensitive in regards to PNE. We evaluated the risk of drug abuse and dependence (DAAD) related to substances that are known to be used for PNE and divided this group into agents with (methylphenidate) and without a known abuse potential outside the field of PNE (atomoxetine, modafinil, acetylcholine esterase inhibitors, and memantine). Reporting odds ratios (RORs) were calculated using a case/non-case approach based on global and country-specific drug safety data from the Uppsala Monitoring Centre (UMC). Both control substances (diazepam and lorazepam) and methylphenidate were statistically associated with DAAD in all datasets (except methylphenidate in Italy). Modafinil was associated with DAAD in the total dataset (ROR, 2.7 (95% confidence interval (CI), 2.2-3.3)), Germany (ROR, 4.6 (95% CI, 1.8-11.5)), and the USA (ROR, 2.0 (95% CI, 1.6-2.5)). Atomoxetine was associated with DAAD in the total dataset (ROR, 1.3 (95% CI, 1.2-1.5)) and in the UK (ROR, 3.3 (95% CI, 1.8-6.1)). Apart from memantine, which was associated with DAAD in Germany (ROR, 1.8 (95% CI, 1.0-3.2)), no other antidementia drug was associated with DAAD. Quantitative signal detection is suitable to detect agents with a risk for DAAD. Its sensitivity regarding PNE is limited, although atomoxetine and modafinil, which do not have a known abuse potential outside PNE, and no antidementia drugs, whose use in PNE is presumably low, were associated with DAAD in our analysis. [ABSTRACT FROM AUTHOR]

Summary: Objective: To verify findings of an independently regulated anterior limbic alpha band source. Methods: In a randomised cross-over study, the spontaneous EEG was recorded in nine healthy subjects after i.v. lorazepam or placebo. Intracerebral current densities within classical frequency bands were estimated with low resolution electromagnetic tomography [LORETA] and compared between groups with t-statistical parametric mapping [SPM{t}]. A region-of-interest [ROI] based method was used to compare frontal and occipital alpha band activity changes. Results: Irrespective of treatment group, local maxima of alpha band power were localised both in the occipital lobe, Brodman area [BA] 18, and in the anterior cingulate cortex [ACC], BA 32. Statistical parametric mapping showed reduced parieto-occipital, but unaltered frontal alpha band power after lorazepam. This result was confirmed by ROI-based comparison of BA 18 and BA 32. Conclusions: There was an anterior limbic maximum of alpha band activity which, unlike occipital alpha, was not suppressed by lorazepam. Significance: The well-known anterior alpha band components may originate from a narrowly circumscribed source, located in the ACC. Frontal and occipital alpha band activities appear to be independently regulated. [Copyright &y& Elsevier]

Background: There is no agreement on the most effective therapy for motor conversion symptoms. Functional electric stimulation has been successfully used to reverse conversion paralysis. We tested the therapeutic potential of high-frequency repetitive transcranial magnetic stimulation (rTMS) in a 20-year-old patient suffering from a conversion paralysis of the right arm.Method: rTMS was applied to the contralateral motor cortex. Stimulations were performed on working days at a frequency of 15 Hz (train length 2 s; inter-train interval 4 s) yielding 4,000 pulses/day.Results: Within 12 weeks, motor function, hyposensibility and muscle bulk were completely restored.Conclusions: The patient recovered completely during rTMS treatment. In addition to possible psychological effects, rTMS may have had a causal therapeutic effect by strengthening corticocortical connections and thereby priming voluntary movements. Further controlled studies are needed. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about aripiprazole and parkinson's disease that appeared in the February 2004 issue of the journal "The American Journal of Psychiatry."

A letter to the editor is presented in response to the article on lithium used in the prevention for suicidal behavior in mood disorder by Andrea Cipriani in the March 2006 issue.

Presents a letter to the editor concerning the use of ziprasidone in treating Parkinson's disease psychosis.

A letter to the editor is presented in response to the article "Psychiatric Hospitalizations Among Survivors of Cancer in Childhood or Adolescence," by Lone Ross, Cristoffer Johansen, S. O. Dalton, and colleagues in the August 14, 2003 issue.

Early studies suggested that the centrally acting non-opioid and non-steroidal analgesic flupirtine (FLP) has no potential for abuse. However, FLP's agonistic effects at the GABAA receptor might prime addictive behaviors, and literature provides some anecdotal reports on FLP abuse/dependence. To shed more light on this topic we acquired and evaluated data obtained from a national German pharmacovigilance database. We analyzed all reports of FLP abuse/dependence that were recorded in the database of the German Federal Institute for Drugs and Medical Devices (BfArM). A total of n = 48 reports of FLP abuse/dependence could be identified (mean age 45 years, 62.5% female). First reports were submitted to BfArM in 1991 with increasing numbers of annual reports from the year 2006 on. Mean daily FLP dosage was 805 mg (range 200-3,000 mg). Current or previous substance abuse/dependence was reported in 21% and 17%, respectively. Mean duration of FLP abuse/dependence until report to BfArM was 23 months (range 1-84 months). Withdrawal syndromes after discontinuation of FLP were reported in n = 9 (19%). Our findings strengthen the hypothesis that FLP features a potential to cause addictive behaviors. Female sex, age >40 years, and long-term FLP-treatment may be possible risk factors for the development of FLP abuse/dependence. [ABSTRACT FROM AUTHOR]

Abstract: Cerebral Amyloidal Angiopathy (CAA), which occurs sporadically in most cases but can also occur hereditarily, belongs to the group amyloidoses and is characterized by the deposition and accumulation of beta-amyloid (Aβ) in smaller arterial vessels of the brain. The deposition of Aβ leads to degenerative changes in the cerebral vessel system (thickening of the vessel wall, microaneurysm, constriction of vascular lumen, dissection), which favour the development of the clinical symptomatology most often associated with CAA. Besides haemorrhages, cerebral ischaemia, transient neurological symptoms, leukoencephalopathy as well as cognitive decline and even dementia may appear in connection with CAA. A definite diagnosis of CAA can only be made on the basis of a pathological assessment, even though diagnostic findings of cerebral neuroimaging and clinical symptoms allow the diagnosis of a probable CAA. At present, no causal therapy options are available. Although CAA is placed within the range of neurological illnesses, psychiatric symptoms such as cognitive impairment, personality change or behavioural problems as well as depression are plausible clinical manifestations of CAA and may even dominate the clinical picture. Apart from epidemiological, pathogenetical, clinical and diagnostical aspects, possible psychiatric implications of CAA are discussed in the review article. [Copyright &y& Elsevier]

Abstract: Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation (rTMS) treatment trials is a central issue. On the one hand, the ideal sham condition should not have a real stimulation effect; on the other hand, it should not be recognized as sham by patients, particularly when considering that real stimulation conditions come along with rTMS specific side effects. Within the course of a multi-centre trial assessing the antidepressant effects of rTMS, patients were randomized to sham or real stimulation, in both cases using a standard stimulation coil. In one centre, patients (n =33) were asked about their impression whether they received the sham or the real treatment, and if they would recommend the treatment to others. 29 patients returned the questionnaires and were included into the analysis. From 15 subjects with real stimulation, 11 suggested to have obtained real, and 4 to have obtained sham. From 14 sham stimulated subjects, 9 suggested to have obtained the real condition and 5 to have been sham stimulated. This difference was not significant (p =0.60, chi square test). In addition, the major part of patients in both stimulation conditions would recommend rTMS to others. In both conditions, real and sham, the majority of subjects believed to have obtained the real condition. This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition. The results imply the feasibility of a valid sham condition with a “real” coil. [Copyright &y& Elsevier]

Purpose: Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC) for assessing the likelihood of AD and AP to cause CAE. Methods: We identified all original medicinal products (OMP) of AD and AP approved in Germany. We searched for their SmPCs using the online services of PharmaNet.Bund, Gelbe liste®, Rote Liste®, Fachinfo-Service®, and via manufacturer contact. We extracted frequencies of reported CAE (QT prolongation, Torsade de Pointes tachycardia, and ventricular arrhythmia) and performed a risk assessment. Results: We obtained the SmPCs of 24 AD and 26 AP identified as OMP. Comparably high reported frequencies regarding QT prolongation were found for Invega® (paliperidone), Serdolect® (sertindole) (≥ 1/100 and < 1/10), and Zoloft® (sertraline) (≥ 1/10.000 and < 1/1000); regarding Torsade de Pointes tachycardia were found for Serdolect® (≥ 1/1000 to < 1/100), Zoloft®, and Trevilor® (venlafaxine) (≥ 1/10.000 and < 1/1000); regarding ventricular tachycardia for Solian® (amisulpride), Xomolix® (droperidol), Zyprexa® (olanzapine), and Trevilor® (≥ 1/10.000 and < 1/1000). Conclusion: The risk and frequency of CAE, as reported in the SmPCs, varied significantly among substances and between groups. There are more reports for AP than AD. The AP with the most frequently reported CAE (QT prolongation and Torsade de Pointes tachycardia) was Serdolect®; for AD, Zoloft® (QT prolongation, Torsade de Pointes tachycardia) and Trevilor® (Torsade de Pointes tachycardia and ventricular tachycardia) carried a higher cardiac risk. [ABSTRACT FROM AUTHOR]

Background: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. Methods: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. Results: Depressed women showed higher SADNESS (t (91.05) = − 3.17, p = 0.028, d = − 0.57) and higher SLC6A4 methylation (t (88.79) = − 2.95, p = 0.02, d = − 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. Conclusions: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression. [ABSTRACT FROM AUTHOR]

Background: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. Methods: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. Results: Depressed women showed higher SADNESS (t (91.05) = − 3.17, p = 0.028, d = − 0.57) and higher SLC6A4 methylation (t (88.79) = − 2.95, p = 0.02, d = − 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. Conclusions: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression. [ABSTRACT FROM AUTHOR]

Background: Volume reductions in brain structures of patients with schizophrenia spectrum disorder (SSD) have repeatedly been found in voxel-based morphometry MRI studies. Hence, an underlying neurodegenerative etiological component of SSD is currently being discussed. In recent years, the imaging method of optical coherence tomography (OCT) has shown its potential in evaluating structural changes in the retina in patients with confirmed neurodegenerative disorders, providing a window into the brain.Methods: Twenty-six patients with schizophrenia or schizoaffective disorder and 23 age- and sex-matched healthy controls were examined with the Heidelberg Spectralis OCT system to derive a single-layer analysis of both retinas. The segmentation of retinal layers was manually corrected to minimize artifacts and software imprecisions.Results: Compared to the control group, SSD patients showed reduced thickness and volume measurements for nearly all retinal layers, and these differences reached significance for macular volume, macular thickness, retinal nerve fiber layer (RNFL) and inner nucleiform layer (INL). Furthermore, a significant correlation between the duration of illness and the total volume of the RNFL was found.Conclusion: Our OCT measurements demonstrate reduced single retinal layer thickness in patients with SSD. In the context of the MRI volume changes, our results provide further evidence that structural changes seen in the brain of patients are also observable in the retina, potentially allowing further insights into the different components of the nervous system that are altered in this highly etiologically complex disorder. [ABSTRACT FROM AUTHOR]

Introduction The neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated to the use of antipsychotics. Since it requires rapid and efficient medical care, high-quality treatment guidelines should be available. In this article, we analyzed and compared different international therapy guidelines for the treatment of schizophrenia, in which NMS treatment recommendations might be contained. Methods We performed an Internet-based search for schizophrenia guidelines via the website of the respective medical society. Guidelines in English, French, Italian, and German from countries whose medical care meets high standards were selected for further analysis and comparison of the NMS treatment recommendations (if present), and their underlying evidence. Results The NMS is mentioned in 12 of 14 guidelines. Only 9 report concrete therapy recommendations (benzodiazepines/dantrolene/bromocriptine/amantadine/intensive care and/or electroconvulsive therapy (ECT)), however, with high heterogeneity. Only 5 guidelines included all possible drug therapy options and ECT, but with differing combination strategies, dosages, application forms, and combinability of options. The level of evidence of the different recommendations was estimated as low. Discussion One-third of the selected guidelines do not report any NMS therapy recommendations. Most guidelines mentioning the NMS do not provide therapy recommendations that include all relevant treatment options. The results show a very high heterogeneity, and the recommendations and statements are of low-evidence levels. The lack of knowledge about the NMS and its treatment may delay the onset of therapy, impair the quality of treatment, and lead to a worse outcome or death. [ABSTRACT FROM AUTHOR]

Objective Malignant catatonia (MC) is an extremely rare, life-threatening disorder. It is characterized by catatonic symptoms accompanied by autonomic instability, hyperthermia, and changes in laboratory values. In many cases, MC is not recognized as such. Evidence-based guidelines are essential to ensure quality of treatment, but what do current national and international guidelines recommend? Method Online search for international guidelines from English-, French-, Italian-, and German-speaking countries whose medical care meets high standards addressing the treatment of MC. These were analyzed and compared regarding statements on MC, recommendations, and strength of scientific evidence. Results Fifteen of the identified guidelines were included. Only 5 of 15 comment on the treatment of MC. As for other rare diseases, no detailed recommendations are available. Suggested therapies are limited to benzodiazepines and electroconvulsive therapy. Levels of evidence and grades of recommendation are predominantly low. Conclusion Many international guidelines do not mention MC. It is not possible to derive a clear algorithm for the treatment of MC from most current guidelines. A thorough update of most guidelines appears to be necessary. Lack of awareness and knowledge of MC among physicians and medical professionals might lead to inadequate or delayed care, worsened outcome, or death. [ABSTRACT FROM AUTHOR]

Background: Recent studies on the pathophysiology of major depression (MD) indicate that degenerative and inflammatory processes may play a role. This finding is supported by magnetic resonance imaging (MRI)-based meta-analysis that show volume reductions in circumscribed areas of the brain in patients with MD. Using optical coherence tomography (OCT), retinal changes have been demonstrated in neurodegenerative disorders. In light of this inflammatory/degenerative hypothesis, we tested whether patients with MD exhibit retinal alterations that might correlate with the severity and duration of the disease.Methods: Patients with MD and age- and gender-matched healthy controls were recruited for the measurement of the total volume and thickness of their retina as well as the thicknesses and volumes of five different retinal layers using single-layer-analysis provided by the spectral-domain-OCT.Results: OCT data from 28 patients with MD and 20 healthy controls were available for evaluation. The exploratory intra-individual group comparison of the two eyes showed a small but significant difference in the retinal total volume (right = 8.69mm3; left = 8.72mm3; p = 0.03) only in patients with MD. There were no other significant differences between the patients with MD and the healthy controls with respect to the OCT measurements.Limitations: The small group size as well as the absence of correction for multiple testing due to the exploratory design should be considered as limitations of our study.Conclusion: While retinal total volume differs between the eyes of patients with MD, the comparison of retinal parameters between these patients and age- and gender-matched healthy volunteers did not show any differences. [ABSTRACT FROM AUTHOR]

To study drug safety and the reporting behavior of adverse drug reactions (ADR) related to agents used for opioid replacement therapy (ORT) we conducted a cross-sectional questionnaire-based telephone survey among physicians who provide outpatient ORT in Germany (n=176; response rate=55.7%). Most respondents (n=97/55.1%) reported that they observe ADR related to buprenorphine, (dihydro)codeine, and (levo)methdone rarely (n=38/21.6%), very rarely (n=39/22.2%) or never (n=20/11.4%). Methadone was reported to be most frequently associated with the occurrence of ADR (n=82/46.6%), followed by levomethadone (n=33/18.8%), buprenorphine (n=6/3.4%), and dihydrocodeine (n=3/1.7%). Frequently observed ADR related to these agents were gastrointestinal, nervous system/psychiatric disorders, and hyperhidrosis. Methadone and levomethadone (not buprenorphine) were frequently associated with fatigue, weight gain, and sexual dysfunction. Hundred twenty nine participants (73.3%) stated that they never report ADR related to ORT; n=19 (10.8%) did so when referring to ADR related to their complete medical practice (X2=141.070; df=1; p<0.001). Similar patterns of ADR related to outpatient ORT as those reported in the product information or in pain therapy were found. Motivation to report ADR related to ORT may be reduced compared to ADR related to the general medical practice. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepress ants. We performed a quantitative signal detection analysis using data from the Uppsala Monitoring Centre from the WHO that records adverse drug reaction (ADR) data from worldwide sources; we retrieved substance- and country-specific (Australia, France, Germany, Italy, Spain, the United Kingdom, and the United States) ADR data and calculated reporting odds ratios as measures for disproportionality within a case/noncase approach. To allow for identification of agents that cause severe forms of hepatotoxic ADRs, we used 2 terms of the MedDRA ('drug-related hepatic disorders-comprehensive search' [DRHD-CS] and '... -severe events only' [DRHD-SEO]). Distribution of signals was heterogeneous throughout the different data sets, and consistent findings were present for only a few substances: agomelatine (AGM) and tianeptine as well as both positive control agents (amineptine, nefazodone) generated signals related to DRHD-CS and DRHD-SEO in all analyzed data sets. Tri- and tetracyclic antidepressants (here amitriptyline, clomipramine, mianserin, mirtazapine, trimipramine) were associated with hepatotoxicity in several data sets. Using 2 MedDRA terms did not allow for detection of agents that cause severe hepatotoxic ADR. Our results support the findings of previous, primarily literature-based, systematic analyses of hepatotoxicity related to antidepressive psychopharmacotherapy. No new safety information could be generated. Application of 2 MedDRA terms did not increase the substance-specific safety information. [ABSTRACT FROM AUTHOR]

Background: Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. Methods: Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. Results: We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. Limitations: Medication use in patients has to be considered as a limitation of our study. Conclusion: Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology. [ABSTRACT FROM AUTHOR]

Inhibition of serotonin uptake in platelets seems to be the crucial mechanism underlying SSRI-associated haemorrhages. This effect is also present in antidepressants featuring non-selective serotonin reuptake inhibition (non-SSRI). Impact of selectivity of serotonin reuptake and/or affinity to the serotonin reuptake transporter on the bleeding risk have not yet been studied sufficiently. We retrieved country- and SSRI-/non-SSRI-specific data from the Uppsala Monitoring Centre and used a case/non-case approach to calculate substance-specific reporting odds ratios (ROR) to evaluate the statistical association of treatment with SSRI/non-SSRI and haemorrhages. Country-specific analysis revealed no clear trends towards an increased risk of bleeding related to particular agents of group SSRI/non-SSRI (sporadically ROR>1 for citalopram, duloxetine, escitalopram, fluvoxamine, paroxetine, sertraline, St. John's wort). There was a clear trend in the total dataset towards a “reduced protective effect” (suggested by ROR<1) on the development of haemorrhages with agents featuring comparatively high affinity to the 5-HTT and/or selective serotonin reuptake inhibition (as with escitalopram, citalopram, duloxetine or venlafaxine) in comparison to agents with lower affinity or non-selective serotonin reuptake inhibition (as with mirtazapine or doxepin). Comparison of group-specific aggregated data (SSRI vs. non-SSRI) revealed significant differences regarding the “protective effect” on the development of haemorrhages between groups SSRI vs. non-SSRI in favour of non-SSRI in nearly all countries as well as in the total dataset. Our findings provide preliminary evidence that agents with increased affinity to the 5-HTT and/or selective serotonin reuptake inhibition may be associated with an increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Since its marketing approval, the attention to the hepatic side-effect profile of the antidepressant agomelatine (AGM) has gradually increased. Several cases of severe hepatotoxic adverse drug reactions (ADR) have been reported and the European Medicines Agency has released a safety warning regarding AGM-associated hepatotoxicity. However, there are insufficient data for an adequate safety assessment of AGM-related hepatotoxicity. Therefore, we performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO that records ADR data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case/non-case approach for AGM and several other antidepressants. AGM was statistically associated with an increased risk of hepatotoxicity (ROR 6.4 [95%CI 5.7-7.2]) as well as both positive controls: amineptine (ROR 38.4 [95%CI 33.8-43.6]) and nefazodone (ROR 3.2 [95%CI 3.0-3.5]). Following amineptine, AGM was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95%CI 3.6-5.3]), mianserin (ROR 3.6 [95%CI 3.3-3.9]), and nefazodone. These results support the hypothesis that AGM is associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance-specific differences regarding the extent of hepatotoxicity. [ABSTRACT FROM AUTHOR]

Patients often bring transitional objects (TO) to inpatient units. The authors quantified the frequency of TO possession in an inpatient psychiatric setting and assessed whether TO use is specific to a personality disorder (PD) diagnosis, focusing on borderline PD (BPD). TO possession was assessed using the Transitional Objects Questionnaire, and PD diagnosis was established using standard DSM-IV clinical interviews. Of the 104 female patients assessed, 57.7% showed TO use; 84% of BPD patients, 71% of BPD-trait patients, 65% of patients with PD traits (other than BPD), and 56% of PD patients (other than BPD) displayed TO use, whereas 30.6% of patients without PD showed TO use. Patients with TOs were significantly younger and had significantly longer hospital stays. The specificity and sensitivity for TO use in the BPD group were 0.506 and 0.84, respectively. The authors conclude that TO use is closely related to PD diagnosis, but is not specific to BPD. [ABSTRACT FROM AUTHOR]

Patients often bring transitional objects (TO) to inpatient units. The authors quantified the frequency of TO possession in an inpatient psychiatric setting and assessed whether TO use is specific to a personality disorder (PD) diagnosis, focusing on borderline PD (BPD). TO possession was assessed using the Transitional Objects Questionnaire, and PD diagnosis was established using standard DSM-IV clinical interviews. Of the 104 female patients assessed, 57.7% showed TO use; 84% of BPD patients, 71% of BPD-trait patients, 65% of patients with PD traits (other than BPD), and 56% of PD patients (other than BPD) displayed TO use, whereas 30.6% of patients without PD showed TO use. Patients with TOs were significantly younger and had significantly longer hospital stays. The specificity and sensitivity for TO use in the BPD group were 0.506 and 0.84, respectively. The authors conclude that TO use is closely related to PD diagnosis, but is not specific to BPD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Female sexual hormones (estrogens and gestagens) may affect neurocognitive functioning and mood. Thus, the use of oral hormonal contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as depression and psychosis. However, the available empiric evidence regarding this connection is conflicting, and, moreover, female sex hormones seem to feature also mood-stabilizing and antidepressive effects. Hence, individual susceptibility factors and preparation-specific pharmacologic properties might play a pivotal role in the development of mood disturbances related to OHC. Single case reports provide empiric data for further systematic approaches. Methods: A clinical case is presented and discussed. Results: A 36-year-old female patient with recurrent major depressive disorder developed rapid relapse in depression after initialization of OHC with ethinyl estradiol 30 μg/chlormadinone acetate 2 mg. This OHC combination was described to particularly feature positive effects on depressive mood. Conclusions: OHC may induce serious mood disturbances and should be administered with care, particularly in patients with affective disorders. [Copyright &y& Elsevier]

A systematic review was conducted to identify the available data for the termKrokodil,which is a jargon expression for an allegedly new drug. Krokodil seems to be a mixture of several substances and was first used in Russia in 2003, with a tremendous increase in the number of addicted individuals since then. The psychoactive core agent of Krokodil is desomorphine, an opioid-analogon that can be manufactured by boiling tablets containing codeine and other ingredients. The procedure results in a suspension that is used intravenously and regularly causes complications such as abscess, thrombophlebitis, and gangrene. [ABSTRACT FROM AUTHOR]

A systematic review was conducted to identify the available data for the termKrokodil,which is a jargon expression for an allegedly new drug. Krokodil seems to be a mixture of several substances and was first used in Russia in 2003, with a tremendous increase in the number of addicted individuals since then. The psychoactive core agent of Krokodil is desomorphine, an opioid-analogon that can be manufactured by boiling tablets containing codeine and other ingredients. The procedure results in a suspension that is used intravenously and regularly causes complications such as abscess, thrombophlebitis, and gangrene. [ABSTRACT FROM AUTHOR]

Previous studies on working memory (WM) function in adults with attention-deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls ( n = 12) and ADHD adults ( n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In order to summarize current knowledge about the drug 'Krokodil' a systematic review including a literature search of the databases PubMed, Embase, Scopus, and Google was conducted in December 2011. According to information acquired, 'Krokodil' is a mixture of several substances and was first reported to have been used in Russia in 2003. The core agent of 'Krokodil' is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself. Self-production results in a contaminated suspension that is injected intravenously. Due to its pharmacologic features, desomorphine shows a high potential to cause dependence. Against the background of first possible cases of 'Krokodil' use in Western Europe, it appears advisable to provide information regarding the fatal consequences of 'Krokodil.' [ABSTRACT FROM AUTHOR]

Abstract: In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain. [Copyright &y& Elsevier]

Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. Methods: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). Results: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found. In two cases fatalities occurred related to PRG nasal use. Conclusions: Even if only little evidence can be found in current literature, the potential for misuse/abuse of PRG via nasal route might be of particular importance in the near future in PRG users who misuse it. Physicians should be aware of these alternative routes of administration. [ABSTRACT FROM AUTHOR]

Focuses on a case of Wilson's disease in psychiatric patients. Patient case background. Inherited disorder of copper metabolism; Complications of Wilson's disease; Hypersomnia in major depression.