[Different number of contraindications between summaries of product characteristics (SmPC) of drugs with the same active ingredients - an analysis of data from SmPCs of neuropsychiatric drugs]. / Unterschiedliche Anzahl von Kontraindikationen zwischen Fachinformationen wirkstoffgleicher Arzneimittel ­ eine Analyse von Daten aus Fachinformationen von neuropsychiatrischen Arzneimitteln.

OBJECTIVE: In the case of prescriptions of pharmaceuticals in the context of the aut-idem-regulation the physician frequently does not know, which same-substance medication is dispensed in the pharmacy; the contemplable same-substance medications may differ in numerous features which raises questions regarding the obligation to give information and medical liability for medical malpractice. Currently, systematic evaluations regarding differences between summaries of product characteristics (SmPCs) of same-substance medications are missing. To determine size and type of those differences SmPCs of most (neuro)psychiatric drugs that are approved in Germany were evaluated regarding the number of listed contraindications (CI). METHODS: Basis for the selection of substances was the Anatomical Therapeutic Chemical (ATC) Classification System (group ATC N Nervous System). Substances that are approved in Germany for the treatment of mental disorders according to ICD-10 F were included. Brand-name medications and SmPCs were searched by means of further in- and exclusion criteria via the online services of PharmNet.Bund, Gelbe Liste, Rote Liste®/Fachinfo-Service® and communication with the manufacturer. RESULTS: N = 941 SmPCs (=116 substances) were evaluated. Considering only the group of SmPCs with > 1 brand-name medication (n = 78; 67.2 %) differences in the number of CIs were found in more than the half of substances (N = 43; 55.1 %). Considering indication groups most groups of SmPCs of same-substance medications with differences in the numbers of CIs were found in - considering only substances with > 1 brand-name medication - hypnotics and sedatives (77.8 %), anxiolytics (75.0 %), drugs for treatment of substance use disorders (66.7 %), antidepressants (61,9 %), anticonvulsant drugs and mood stabilizers (53.8 %), followed by antipsychotics (41.2 %), antidementia-drugs (20.0 %), and psychostimulants (0 %). Largest ranges regarding the number of CIs were found in the SmPCs of morphine (14), amitriptyline (8), chlorprothixene (6), lorazepam (6) and citalopram (4). CONCLUSION(S): In numerous (neuro-)psychopharmacologic substances differences exists between the SmPCs of the associated same-substance medications regarding the number of CIs. Due to the outstanding evaluation of content aspects of these differences and legal evaluation the relevance of this result for clinical practice is not yet clear.

Longer Duration of Untreated Psychosis is Associated with Poorer Outcomes for Patients with Delusional Infestation.

We examined the association between the duration of untreated psychosis and outcome for patients with delusional infestation. This multi-centre international study included 211 consecutive patients. Illness severity was evaluated at first presentation and outcome was measured with the Clinical Global Impression scale (CGI) at baseline and follow-up. A regression analysis showed a clear clinical and statistically significant association between shorter duration of untreated psychosis and better outcome at follow-up. Patients with a duration of untreated psychosis of less than one year showed a CGI-S change from 5.37 to 2.07; those with a duration of untreated psychosis of 1-5 years a change from 5.48 to 2.59, and those with a duration of untreated psychosis of >5 years a change from 5.59 to 3.37. This difference of 1.1 CGI points between the groups resembles a clinically relevant difference in patient outcome. Our results suggest that longer duration of untreated psychosis in patients with delusional infestation is associated with significantly less favour-able clinical outcomes.

[Psychiatric Emergencies in the Preclinical Emergency Medicine Service in Ulm, Germany in 2000 and 2010, and Practical Consequences]. / Psychiatrische Notfälle im Notarzt- und Rettungsdienst in Ulm in den Jahren 2000 und 2010 und Konsequenzen für die Praxis.

Background Psychiatric emergencies (PE) in preclinical emergency medical services are about 5 - 10 % of all emergencies and represent often a source of difficulties in handling for the non-psychiatric professional helpers that deal with them. Studies informing about quantitative and qualitative changes of PEs in preclinical emergency medicine in Germany are scarce. Methods Therefore, we conducted a retrospective cross-sectional study of PE in a preclinical emergency medical service based on the protocols of the emergency ambulance of the Section for Emergency Medicine at the University Hospital Ulm comparing the years 2000 and 2010. Results We observed a significant increase of PEs from 8.8 % in the year 2000 (n = 285, from a total of n = 3227) to 10.3 % in 2010 (n = 454, from a total of n = 4425). In both years intoxications were the most common PE [2000: n = 116 (44.4 %); 2010: n = 171 (37.7 %)], followed by suicide-related behavior [2000: n = 59 (22.6 %); 2010: n = 78 (17.2 %)] and acute anxiety disorders [2000: n = 37 (13 %); 2010: n = 105 (23.1 %)]. The mentioned three conditions accounted for about 80 % of all PE. Most frequently PE occurred at the weekend and with the highest density in the evening and at night (18 - 24 h) in both years. Patients with PE were predominantly men, but the rate of women causing PE increased between 2000 and 2010. Discussion/Conclusion This study provides preliminary data on current trends in PEs in preclinical emergency medicine in Germany and has implications for improving the medical care provided.

Mild Hypothermia in a Child with Low-Dose Risperidone.

Risperidone is a widely used, second-generation antipsychotic approved for treating schizophrenia as well as for treating aggression in children and adolescents with mental retardation. The substance has a well-established risk profile including alterations of body temperature. Apart from hyperthermia with and without full-blown malignant neuroleptic syndrome, low body temperatures (hypothermia) have also been reported anecdotally, usually appearing in the context of comedication. Here, we report a case of hypothermia associated with a low-dose risperidone monotherapy in a child.

Frequency of delusional infestation by proxy and double delusional infestation in veterinary practice: observational study.

BACKGROUND: Nothing is known about the prevalence of delusional infestation in veterinary practice and the consequences for psychiatrists. AIMS: We attempted to examine the frequency of delusional infestation among pet owners presenting their animals to veterinary clinics. METHOD: We conducted a survey among 32 663 veterinary clinicians who were members of the Veterinary Information Network. RESULTS: The respondents had seen 724 suspected cases of delusional infestation by proxy in a pet. The clients were mainly White, female and 30-60 years old. They presented mainly dogs and cats, and the alleged infestation was mainly with arthropods or worms. Also, 252 clients claimed to be affected themselves; we termed this 'double delusional infestation'. CONCLUSIONS: Delusional infestation is seen frequently in veterinary practice. Psychiatrists need to be aware that patients may have pets they believe are infested.

Abuse liability of centrally acting non-opioid analgesics and muscle relaxants--a brief update based on a comparison of pharmacovigilance data and evidence from the literature.

There is a lack of data regarding the abuse liability of centrally acting non-opioid analgesics (NOA) and muscle relaxants (MR). A comparison of data retrieved from a German pharmacovigilance database (BfArM; accessed May 2013) and data from the literature concerning the abuse liability of NOA and MR approved in Germany was performed. The BfArM-database demonstrated cases of abuse only for clonidine and paracetamol, whereas the literature suggests evidence for an abuse potential of baclofen, clonidine, ketamine, metamizole, methocarbamol, orphenadrine, paracetamol, propyphenazone, and tizanidine. The low number of detected cases in the BfArM-database could be a result of under-reporting.

Safety of electroconvulsive therapy in the presence of cranial metallic objects.

OBJECTIVES: Little is known regarding the safety of electroconvulsive therapy (ECT) in the presence of cranial metallic objects (cMO) such as medical devices or metallic foreign bodies. The presence of cMO raises 3 theoretical concerns toward the safety of ECT: (1) cMO may significantly alter the ECT-induced electric field distribution in the brain regarding field strength and focality, (2) vascular complications at the location of the cMO due to the ECT-induced hyperdynamic state may occur, and (3) possible development of a prolonged seizure/status epilepticus during ECT as a consequence of a device-induced symptomatic epilepsy. In the light of missing systematic approaches, we intended to assess the safety of ECT in the presence of cMO with particular regard to the concerns as specified previously. METHODS: A systematic review of previously published cases of ECT in patients with cMO was conducted. RESULTS: We identified 23 publications reporting 24 cases of ECT in the presence of cMO (cerebral clipping systems, 8 cases; cerebral coils, 2 cases; deep brain stimulator, 4 cases; osteosynthesis materials or other metallic medical devices, 7 cases; foreign bodies, 3 cases). Modified placement of ECT-electrodes was reported in 10 cases (42%). No ECT-related complications with regard to the proposed theoretical concerns were reported. CONCLUSIONS: The absence of cMO-related complications during ECT in the reported cases implies that cMO might not represent an absolute contraindication for the performance of ECT. However, the indication for ECT should be put in place thoroughly in patients with cMO. Further research is necessary for an adequate safety assessment.

Pregabalin abuse and dependence in Germany: results from a database query.

PURPOSE: Pregabalin (PRG) is approved for the treatment of neuropathic pain, partial seizures and generalised anxiety disorder in many countries and currently under study for other indications. Supported by case reports and the results of a limited number of studies there is an ongoing debate on the potential of PRG to cause addictive behaviours. However, currently available evidence on this issue is sparse, and any definitive assessment of PRG's potential for abuse and dependence is not yet in sight. The aim of our study was to identify the number of cases of PRG abuse or dependence reported to the database of a German medical regulatory body and to obtain insights into further usage-specific parameters. METHODS: We conducted a query of the entire database of the German Federal Institute for Drugs and Medical Devices (BfArM) regarding reports of PRG abuse or dependence and analysed these cases on the basis of several parameters. RESULTS: A total of 55 reports of PRG abuse or dependence were identified (mean age 36 years, 64 % of reports involved males). The first reports were submitted to BfArM in 2008, and the reporting frequency has increased up to the present. Mean daily PRG dosage was 1424 mg. Current or previous polytoxicomania was present in 40 and 42 % of cases, respectively. Psychiatric diagnoses other than substance-related disorders were reported in 13 (24 %) cases. In about one-third of the patients withdrawal syndromes subsequent to discontinuation of PRG were reported. CONCLUSIONS: Cases of PRG abuse or dependence have been reported to the BfArM since 2008, with a marked increase of such reports in subsequent years. Male sex and a history of polytoxicomania may be possible risk factors for the development of addictive behaviours related to PRG.

"Krokodil":revival of an old drug with new problems.

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."

Delusional infestation.

This papers aims at familiarizing psychiatric and nonpsychiatric readers with delusional infestation (DI), also known as delusional parasitosis. It is characterized by the fixed belief of being infested with pathogens against all medical evidence. DI is no single disorder but can occur as a delusional disorder of the somatic type (primary DI) or secondary to numerous other conditions. A set of minimal diagnostic criteria and a classification are provided. Patients with DI pose a truly interdisciplinary problem to the medical system. They avoid psychiatrists and consult dermatologists, microbiologists, or general practitioners but often lose faith in professional medicine. Epidemiology and history suggest that the imaginary pathogens change constantly, while the delusional theme "infestation" is stable and ubiquitous. Patients with self-diagnosed "Morgellons disease" can be seen as a variation of this delusional theme. For clinicians, clinical pathways for efficient diagnostics and etiology-specific treatment are provided. Specialized outpatient clinics in dermatology with a liaison psychiatrist are theoretically best placed to provide care. The most intricate problem is to engage patients in psychiatric therapy. In primary DI, antipsychotics are the treatment of choice, according to limited but sufficient evidence. Pimozide is no longer the treatment of choice for reasons of drug safety. Future research should focus on pathophysiology and the neural basis of DI, as well as on conclusive clinical trials, which are widely lacking. Innovative approaches will be needed, since otherwise patients are unlikely to adhere to any study protocol.

Morgellons in dermatology.

Delusional parasitosis (DP) is the most frequent delusional disorder in dermatology. In DP there is a fixed belief of a usually skin-related invasion or infestation by a number of alleged infectious species (usually parasites and bacteria), whose identity has varied over the decades. Since 2002 worldwide an increasing number of patients have complained of unverifiable fibers and filaments in or on the skin, associated with numerous nonspecific complaints (arthralgias, altered cognitive function and extreme fatigue). This entity has been named "Morgellons disease" by the patients themselves, although medical evidence for its existence is lacking. As an example, we discuss a 55-year-old woman who complained of Morgellons disease and was treated as if she had DP. Currently the delusional assumption of infestation with Morgellons should be considered as a new type of DP with some kind of inanimate material. We therefore recommend in case of DP including Morgellons the use of the broader term "delusional infestation".

[Use of summaries of product characteristics (SmPC) among family doctors and pharmacists in the context of the aut-idem regulation: Results of an exploratory cross-sectional survey]. / Nutzung von Fachinformationen bei Hausärzten und Apothekern im Zusammenhang der Aut-idem-Regelung: Ergebnisse einer explorativen Querschnittsbefragung.

INTRODUCTION: Summaries of product characteristics (SmPC) of same-substance medications may feature content-related differences. This may cause difficulties regarding informed consent in the case of prescriptions of drugs in the context of the aut-idem regulation. A survey among family doctors (FD) and pharmacists (PH) was conducted in order to evaluate the usage behaviour of SmPCs, sources used to obtain information about drugs and the awareness of the existence of differences between SmPCs of same-substance medications. METHODS: An exploratory/non-representative, questionnaire- and telephone-based, semi-structured cross-sectional survey was performed (June to August 2018). RESULTS: Participation rate of FD and PH was 29.8 % (34/114) and 73.0 % (73/100), respectively. In the previous month, all PH and 82.4 % of FD said that they had used a SmPC at least once (p=0.001). FD used SmPCs 6.4±4.9 and PH 65.0±52.5 times a month (p<0.001). In both occupational groups SmPCs were used most frequently to obtain information about dosing and/or type of application (FD: 97.1 %; PH: 98.6 %) and contraindications (97.1 % and 86.3 %, resp.). In both samples, the internet was the most frequently used drug information source (FD: 97.1 %; PH: 98.6 %), followed by the Rote/Gelbe Liste (97.1 % and 71.2 %, resp.) and the SmPCs of the original product (52.9 % and 65.8 %, resp.) or generic drug (52.9 % and 61.6 %, resp.). Only 32.4 % of the FD vs. 79.5 % of PH believed that differences might exist between SmPCs of same-substance medications (p<0.001). FD stated that they never (11.8 %) or rarely (85.3 %) use SmPCs for informed consent. It was indicated that the aut-idem substitution is excluded in 10.3 %±5.0 (FD) and 9.6 %±6,1 (PH) of issued or received prescriptions. DISCUSSION: The results of the present survey indicate a low utilization rate of SmPCs by FD and little awareness of the existing differences of SmPCs of same-substance medications in this occupational group. Both aspects may impede proper information of patients, particularly in cases of aut-idem prescriptions of substances for which many same-substance medications with different SmPCs are available. CONCLUSION: Physicians should use SmPCs regularly and keep themselves informed about differences between SmPCs of same-substance medications.

Retinal single-layer analysis with optical coherence tomography (OCT) in schizophrenia spectrum disorder.

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.

Abnormal cerebellar volume in somatic vs. non-somatic delusional disorders.

BACKGROUND: There is abundant evidence for cerebellar involvement in schizophrenia, where the cerebellum has been suggested to contribute to cognitive, affective and motor dysfunction. More recently, specific cerebellar regions have also been associated with psychotic symptoms, particularly with auditory verbal hallucinations. In contrast, little is known about cerebellar contributions to delusions, and even less is known about whether cerebellar involvement differs by delusional content. METHODS: Using structural magnetic resonance imaging at 1.0 T together with cerebellum-optimized segmentation techniques, we investigated gray matter volume (GMV) in 14 patients with somatic-type delusional disorder (S-DD), 18 patients with non-somatic delusional disorder (NS-DD) and 18 patients with schizophrenia (SZ) with persistent non-somatic delusions. A total of 32 healthy controls (HC) were included. Between-group comparisons were adjusted for age, gender, chlorpromazine equivalents and illness duration. RESULTS: Compared to HC, S-DD patients showed decreased GMV in left lobule VIIIa. In addition, S-DD patients showed decreased GMV in lobule V and increased GMV in bilateral lobule VIIa/crus II compared to NS-DD. Patients with SZ showed increased GMV in right lobule VI and VIIa/crus I compared to HC. Significant differences between HC and NS-DD were not found. CONCLUSIONS: The data support the notion of cerebellar dysfunction in psychotic disorders. Distinct cerebellar deficits, predominantly linked to sensorimotor processing, may be detected in delusional disorders presenting with predominantly somatic content.

Second-generation antipsychotics in primary and secondary delusional parasitosis: outcome and efficacy.

In the absence of controlled clinical trials, little is known about antipsychotic treatment in primary and secondary delusional parasitosis (DP). All available data on the efficacy of antipsychotics (APs) and the outcome in DP date back to the era of first-generation antipsychotics, whereas such data are lacking for second-generation antipsychotics (SGAs). To study outcome and efficacy of SGAs in all forms of DP by means of a case-based analysis, we extracted 63 cases from 434 available publications and assessed them by 2 independent raters using standardized criteria for efficacy and outcome. The time course of response and the SGA doses used in DP were also first studied. The sample was comparable to classic samples and comprised mainly secondary DP cases (56%). The median onset of effect occurred after 1.5 weeks, and the maximum effect occurred after 6 weeks (later in primary than secondary DP, 10 vs 3 weeks; P < 0.004). If a treatment of more than 8 weeks could be established, all cases responded at least partially. In the outcome analysis, partial or full remission was performed by 75% of cases (final outcome, therapy switches allowed). In the efficacy analysis, partial or full remission was reached in 69% of the situations when an SGA was introduced (without therapy switches). Secondary DP was more likely to respond to SGAs than primary DP (78% vs 59% trend). Risperidone and olanzapine were most widely used and resulted in full or partial remission in 69% and 72%, respectively. Doses were lower than those used in schizophrenia. This first retrospective case-based study provides low-level evidence that SGAs are effective in DP and that outcome is favorable, although a publication bias is likely. Our findings need to be confirmed by controlled trials.

Striatal lesions in delusional parasitosis revealed by magnetic resonance imaging.

INTRODUCTION: Delusional parasitosis (DP) is a syndrome characterized by the firm conviction that small living beings infest the skin. The etiology can be primary and secondary. Structural brain abnormalities in DP have only been reported in case reports often subcortical vascular encephalopathy and right-hemisphere strokes in the temporo-parietal cortex. Systematic brain imaging studies are lacking. We aimed to identify a brain region with structural lesions in patients with DP in order to better understand the pathophysiology of DP. METHODS: Nine consecutive patients with DP in a psychiatric outpatient department were assessed clinically and by means of cranial magnetic resonance imaging (MRI). RESULTS: Five of the nine cases were diagnosed as having DP as psychotic disorders due to a general medical condition while three had DP arising from pre-existing psychiatric illness and one suffered from a delusional disorder, somatic type (primary form). Four of the five DP cases secondary to a general medical condition (one case could not be analyzed) had striatal lesions predominantly in the putamen. Thalamic or cortical lesions were found in one case, respectively. In the primary DP case and all cases secondary to another psychiatric disorder basal ganglia and subcortical gray matter lesions were absent. In all medical (secondary) DP cases subcortical white matter lesions were found mainly in the centrum semiovale. Three of the five medical DP cases showed severe generalized brain atrophy which was absent in the primary DP case and in the cases secondary to other psychiatric disorders. DISCUSSION/CONCLUSION: We present the findings of the first structural MRI study in DP. Our results suggest a possible relevance of structural lesions in the striatum, predominantly the putamen, in the medical (secondary) DP-subgroup. Our findings are in line with other studies demonstrating that the putamen, in addition to its role in motor regulation, represents a brain area that mediates visuo-tactile perception. Disturbed functioning of the putamen and associated brain areas of the somatic/dorsal striato-thalamo-cortical loop might therefore play an important role in the pathophysiology of DP, which is characterized by somatic delusions, tactile misperceptions and sometimes also visual hallucinations. The involvement of the striatum and the efficacy of antidopaminergic antipsychotics indicate dopaminergic dysfunction in DP. Evidence from DP in intoxication with substances influencing the dopamine transporter (DAT) (e.g. cocaine, methylphenidate, bupropion) further supports this observation. Further neuroimaging studies in larger samples are needed to expand our preliminary knowledge obtained from this case-series study.