Roland W. Freudenmann

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.

Accuracy of stereotaxic positioning of transcranial magnetic stimulation

Summary:In cognitive neuroscience, optically tracked frameless stereotaxic navigation has been successfully used to precisely guide transcranial magnetic stimulation (TMS) to desired cortical areas for brain-mapping purposes. Thereby, potential sources of imprecision are the fixation of a reference frame to the head of the subject and the referencing procedure according to certain landmarks (LM). The aim of our study was to evaluate the accuracy of frameless stereotaxic coil positioning in a standard experimental setting. A parameter for accuracy is the reproducibility of LM coordinates. In order to test the stability of the referencing for stereotaxic positioning within a single TMS session (within-session stability), the coordinates of six predefined facial LM in nine subjects were recorded first after the initial registration and second after a 20 minutes TMS session. The two sets of coordinates were then compared. The reliability of the positioning coordinates between different TMS sessions (inter-session repeatability) was addressed by registering the subjects LM coordinates in two independent TMS sessions. The variance of the recorded coordinates was analyzed. Altogether, LM were registered 1728 times (192 measures per subject). Within-session stability: The mean Euclidean distance (MED) between the LM position coordinates before and after a TMS session was 1.6 mm, when pooling over all LM. Inter-session repeatability: The MED between the LM positions recorded after the reference procedures of two different sessions showed an average deviation of 2.5 mm. In conclusion, optically tracked frameless stereotaxic coil positioning is from the technical viewpoint of high stability and repeatability. It is therefore a precise method for TMS brain mapping studies or for repeated TMS treatments, with the need of topographically exact stimulation.

Delusional parasitosis: a new pathway for diagnosis and treatment

Delusional parasitosis is an uncommon disorder that presents particular challenges to the dermatologist. Patients often resist psychiatric referral. Evidence of efficacy of treatment options is generally weak, but some studies exist. By identifying whether the disorder is primary or secondary to another illness, by attempting to involve the liaison psychiatry team if possible and by treating the patient with a modern antipsychotic, remission is achievable. A pathway for diagnostics and therapy is presented. Treatments of choice are ‘atypical’ or second‐generation antipsychotics such as amisulpride, risperidone or olanzapine in age‐appropriate doses. Pimozide is no longer the treatment of choice, owing to a higher risk of adverse drug reactions and lower concordance. In some cases, depot antipsychotics can be considered. For diagnostics and treatment, close collaboration of dermatologists and psychiatrists is recommended.

Neural Correlates of Error Monitoring Modulated by Atomoxetine in Healthy Volunteers

BACKGROUND Atomoxetine is a selective norepinephrine reuptake inhibitor clinically used for treatment of attention-deficit/hyperactivity disorder. In healthy control subjects, doses of 40 mg or 60 mg improved inhibitory control in combination with modulation of prefrontal cortex functioning. We investigated the effects of atomoxetine (80 mg) on error monitoring as a second key component of cognitive control. METHODS Twelve healthy, male volunteers were included in a randomized double-blind, placebo-controlled, within-subjects design to examine the effects of a single dose of atomoxetine on neural activities during a combined Eriksen flanker-Go/NoGo task as measured by functional magnetic resonance imaging. RESULTS Behaviorally, atomoxetine led to a significant increase in failed inhibition. Functionally, interaction analysis revealed a significant increase of the error signal (incorrect minus correct NoGo trials) under atomoxetine in bilateral inferior frontal cortex and presupplementary motor area. Drug-dependent increases in error signaling did not correlate with increased error rates. Analysis of neuropsychological data indexed a significant increase in phasic alertness. CONCLUSIONS Results support that atomoxetine increases neural sensitivity for errors in healthy control subjects, possibly due to an accentuated representation of the task set. However, this gain was accompanied by deterioration in inhibitory control, possibly reflecting a shift beyond the optimal working range of the norepinephrine system.

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.

Delusional infestation: neural correlates and antipsychotic therapy investigated by multimodal neuroimaging.

INTRODUCTION In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging. METHODS In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM). RESULTS In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy. DISCUSSION/CONCLUSION Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI.

Desomorphine Goes “Crocodile”

A systematic review was conducted to identify the available data for the term Krokodil, 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.

Delusional infestation and the specimen sign: a European multicentre study in 148 consecutive cases.

Background  Systematic studies of delusional infestation (DI), also known as delusional parasitosis, are scarce. They lack either dermatological or psychiatric detail. Little is known about the specimens that patients provide to prove their infestation. There is no study on the current presentation of DI in Europe.

Concerns About Pregabalin: Further Experience With Its Potential of Causing Addictive Behaviors

Pregabalin (PRG) is approved for the treatment of neuropathic pain, partial seizures, and generalized anxiety disorder in many countries. Supported by case reports and a few studies there is an ongoing debate on PRGs potential to cause addictive behaviors. Considering that PRG is currently under investigation for the treatment of benzodiazepine dependence and withdrawal as well as relapse prevention in alcohol dependence, assessment of PRGs abuse and dependence potential is indispensable. We report the case of a 38-year-old female patient with borderline personality disorder and past alcohol abuse who developed PRG abuse. The patient took up to 800 mg PRG per day, initially administered to treat unspecific anxiety, and experienced euphoric feelings after PRG intake. In the further course, she increased the daily PRG dosage and consulted other physicians to receive additional PRG prescriptions. During reduction of PRG, the patient developed a moderate withdrawal syndrome with vegetative symptoms. Because of the early detection of the developing PRG abuse (4 months after first application of PRG), the development of PRG dependence was prevented. This case illustrates the possibility of PRG to trigger the development of addictive behaviors and should encourage physicians to be very careful when administering PRG to patients with current or past substance-related disorders.

Agomelatine and hepatotoxicity: implications of cumulated data derived from spontaneous reports of adverse drug reactions.

Considering the antidepressant agomelatine (AGM) there is a discrepancy between the widespread knowledge of the potential of AGM to cause hepatotoxic adverse drug reactions (ADR) and the availability of corresponding published data. This impedes an adequate assessment of the hepatotoxicity profile of AGM. We conducted a query of the database of a German Medical Regulatory Body (BfArM) and analyzed spontaneous reports of hepatotoxic ADR. We identified n=58 cases of AGM-related hepatotoxic ADR. Most frequent ADR was asymptomatic increase of liver enzymes (79%); n=6 patients (10%) with AGM-related toxic hepatitis were reported. Characteristics of patients: female sex (69%), age > 50 years (mean 54 years), polypharmacy (57%), and presence of cardiovascular risk factors (58.5%). Most of the hepatotoxic ADR (90%) were reported to have improved/recovered after discontinuation of AGM. Our evaluation suggests that AGM features a potential to cause severe forms of hepatotoxicity and emphasizes that a pre-existing liver disease is a contraindication for treatment with AGM. Secondly, increased age, female sex and polypharmacy may be risk factors for the development of AGM-related hepatotoxic ADR.