Long-term use of benzodiazepines in chronic insomnia: a European perspective

Chronic insomnia occurs in ~10% of the general population and has numerous negative health effects. The recommended first line treatment of cognitive behavior therapy for insomnia is not widely available for patients in Europe, so pharmacotherapies such as benzodiazepine receptor agonist agents (benzodiazepines and Z-drugs) are commonly used. However, their use is only recommended for ≤4 weeks due to unproven long-term efficacy in treatment of chronic insomnia, and the risk of tolerance, and the potential for dependence and misuse. In Europe, recommendations limiting the use of benzodiazepines (lowest dose and shortest duration) in chronic insomnia are not always followed, likely due to the lack of approved effective alternative therapies. Here we present a recent pilot survey of the pharmacological treatment landscape in chronic insomnia in five European countries (France, Germany, Italy, Spain, and the United Kingdom) and physicians’ attitude toward treatment. The results suggest that benzodiazepines and Z-drugs are the most widely used treatments in chronic insomnia and are being used for longer than their recommended duration. Country variations in prescription rates were observed. Due to the known association between long-term benzodiazepine use and potential for developing dependence, further analysis of the literature was performed on the use and misuse of benzodiazepines. The results show that long-term use of benzodiazepines is associated with multiple consequences of treatment, including dependence, but also that previous use of benzodiazepines may increase the risk of opioid use disorder

Risk Attitudes and Birth Order

Risk attitudes play important roles in health behavior and everyday decision making. It is unclear, however, whether these attitudes can be predicted from birth order. We investigated 200 mostly male volunteers from two distinct settings. After correcting for multiple comparisons, for the number of siblings and for confounding by gender, ordinal position predicted perception of health-related risks among participants in extreme sports (p < .01). However, the direction of the effect contradicted Adlerian theory. Except for alcohol consumption, these findings extended to self-reported risk behavior. Together, the data call for a cautious stand on the impact of birth order on risk attitudes

Daytime sleepiness in patients with untreated restless legs syndrome

Background Restless legs syndrome (RLS), a disorder characterized by an urge to move one’s legs during sleep or rest, leads to impaired sleep quality. Many patients with RLS report increased daytime sleepiness, but this has seldom been the focus of clinical research. The current study empirically investigated the prevalence and severity of daytime sleepiness in RLS. Methods This prospective study included 29 newly diagnosed treatment-naïve patients with RLS and 31 healthy controls and assessed standardized subjective (tiredness symptom scale [TSS], Stanford Sleepiness Scale [SSS], Epworth Sleepiness Scale [ESS]), cognitive (psychomotor vigilance task [PVT], Mackworth Clock Test [MCT]), and physiological measures (pupillary unrest index [PUI]). RLS symptom severity was assessed, and the effects of RLS on general health aspects and subjective sleep quality (Pittsburgh Sleep Quality Index) were compared to control data. Results Patients had moderate to severe RLS with significant negative effects on general health, quality of life, and sleep quality. Patients with RLS showed more subjective daytime sleepiness (ESS) and current sleepiness (TSS, SSS) than controls. The objective performance of patients in sustained attention tasks (P VT, MCT) was significantly worse than that of controls. Additionally, patients showed higher PUI scores. Conclusion In the present study, RLS was associated with markedly impaired subjective sleep quality and with subjectively and objectively increased daytime sleepiness. Since daytime sleepiness can be a major factor leading to compromised quality of life, assessing and treating sleepiness should be incorporated into standard diagnostics and treatment

Cariprazine in the management of negative symptoms of schizophrenia : state of the art and future perspectives

In schizophrenia, dopaminergic hyperactivity in the mesolimbic regions, or possibly even selectively so in the dorsal striatum, seems to cause the emergence of psychotic symptoms, whereas dopaminergic hypoactivity in cortical regions underlies the negative symptoms and cognitive deficits. Managing the negative symptoms is a major current challenge in the treatment of schizophrenia with a dearth of novel modalities to address this clinical issue. Cariprazine is a novel second-generation antipsychotic that specifically targets the D3 receptor mainly associated to negative symptoms. The review summarizes the main issues regarding negative symptom management and the role of cariprazine treatment

Moral Reasoning in Psychopaths

Patienten mit der psychischen Störung „Psychopathie&ldquo; zeigen ein Muster von emotionaler Abgestumpftheit, Impulsivität und unmoralischem Verhalten. Zur Untersuchung moralischen Urteilens wurden in der vorliegenden Studie alltagsrelevante Konflikte mit moralischem bzw. neutralem Inhalt entwickelt und 12 „psychopathischen&ldquo; forensischen Patienten sowie 12 nicht-psychopathischen forensischen Patienten präsentiert. „Psychopathische&ldquo; im Vergleich zu nicht-psychopathischen Patienten berichteten signifikant positivere Gefühle bei unmoralischen Entscheidungen als Nicht-Psychopathen. Außerdem wurden in der Gruppe der „Psychopathen&ldquo; im Vergleich zu den Nicht-Psychopathen signifikant häufiger unmoralische Entscheidungen auf moralische Konflikte getroffen. Diese Befunde deuten darauf hin, dass eine Störung der Emotionsverarbeitung ursächlich für dissoziales Verhalten bei „Psychopathen&ldquo; sein könnte.Psychopathic patients show a behavioral pattern that is characterized by indifference, impulsivity and antisocial behavior. To investigate moral reasoning we developed conflicts of everyday life with either moral or neutral content. These conflicts were then presented to a group of 12 psychopathic forensic patients as well as to a group of 12 non-psychopathic forensic patients.Psychopathic compared to non-psychopathic patients reported significantly higher positive feelings when choosing an immoral response alternative than non-psychopaths. Furthermore, psychopaths picked significantly more often an immoral response alternative in the conflicts with moral content than did the non-psychopaths. These results indicate that impairment in emotional processing abilities may be at the core of antisocial behavior in psychopathy

NISAS-2000 - die "Nationwide Insomnia Screening and Awareness Study": Insomnien und Schlafstörungen in der allgemeinärztlichen Versorgung

ZIEL: Ermittlung der Stichtagsprävalenz von Insomnie und anderen Schlafstörungen in deutschen Allgemeinarztpraxen sowie Bestimmung hausärztlicher Erkennensraten. METHODIK: Bundesweite Zufallsauswahl von 539 Arztpraxen. Charakterisierung der Arzt- und Praxismerkmale mittels initialer Vorstudie. Darauf folgend eine Stichtagsbefragung aller Hausarzt-Patienten mittels Schlaffragebogen (PSQI) und klinischen Fragen (N = 19155 Fälle) sowie klinisch-ärztliche Beurteilung durch den behandelnden Artz mittels CGI und Fragebogen. ERGEBNISSE: 1. Trotz nur moderater Kompetenzeinschätzungen hinsichtlich Diagnose und Therapie behandeln Hausärzte Insomnien und andere Schlafstörungen vorwiegend selbst, auch wenn diese einen hohen Behandlungsaufwand erfordern. 2. Die Stichprobe kann als typisch für die Hausarzt-Klientel angesehen werden. 3. Schlafstörungen sind der dritthäufigste Konsultationsanlass. Nahezu jeder zweite Patient berichtete, in den vergangenen 2 Wochen unter Schlafbeschwerden gelitten zu haben, 26,5% erfüllten aufgrund der subjektiven Angaben die Studienkriterien (DSM-IV) für Insomnie. 4. Auch die Ärzte beurteilten 46,4% aller ihrer Patienten mittels CGI zumindest als Grenzfälle einer Schlafstörung, 85,6% wurden als chronisch eingeordnet. Die ärtzlich beurteilte Insomnieprävalenz betrug 25,9%, die anderer Schlafstörungen 13,7%. 5. Nur 54,3% aller Insomniepatienten wurden auch als solche vom Hausarzt diagnostiziert. DISKUSSION: Die Studie liefert erstmals bundesrepräsentative, differenzierte epidemiologische Daten zu der Prävalenz, dem Schweregrad, den Einschränkungen und den Verlaufsmustern von Insomnien und Schlafstörungen. Die außerordentlich große Häufigkeit und die zum Teil markanten Defizite hinsichtlich Erkennen und Diagnostik in der primärärztlichen Versorgungen werden diskutiert.AIM: To estimate the point prevalence of insomnia, recognition and prescription behavior in primary care. METHODS: Nationwide sample of 539 primary care settings along with their characterization (stage 1). Standardized assessment of all attenders (N = 19.155 patients) on the NISAS target day using a sleep questionnaire (PSQI) and additional questions to cover psychosocial and additional clinical variables. All patients were evaluated by the primary care doctors using a standardized clinical appraisal questionnaire, including a CGI-rating. RESULTS: Prevalence insomnia according to DSM-IV was 26.5%. Recognition of presence of any clinically significant sleep disorder was 72%, recognition of insomnia was poor 54.3%. 85.6% of insomnia patients were rated as chronic. Close to 50% of all insomnia cases did not receive a specific insomnia therapy. Herbals, followed by hypnotics and sedatives and antidepressants were the three most frequent treatments applied, psychotherapy was only seldomly indicated. DISCUSSION: NISAS provides for the first time nationally representative estimates of interventions for insomnia in primary care. The relatively low treatment rates and the high proportion of chronic patients receiving longterm prescription of benzodiazepines seem to be critical. Priorities for future agenda to improve this situation are discussed

Amygdalohippocampal neuroplastic changes following neuroleptic treatment with quetiapine in first-episode schizophrenia

Schizophrenia is a severe, debilitating, chronic disease that is accompanied by morphologic changes within the brain. However, it is unclear to what extent alterations of grey and white matter in schizophrenia are linked to the disease itself, or whether they are a consequence of neuroleptic treatment. Typical and atypical antipsychotics exert differential effects on brain structure. Moreover, atypical antipsychotics may have distinct profiles with respect to grey matter in schizophrenic patients. Findings on drug-induced grey matter changes are heterogeneous due to variation in stage of illness, duration of treatment and use of multiple antipsychotics. Using voxel-based morphometry applied to high-resolution magnetic resonance images, we show that monotherapy with the atypical agent quetiapine (mean daily dose = 445 mg ± 200 s.d.) may induce structural brain changes in first-episode schizophrenia patients (N = 20) within 21 d of treatment. Specifically, we demonstrate longitudinal macroscopic changes (i.e. grey matter increases) in the left amygdalohippocampal region that were predicted by drug plasma levels but not daily doses. These structural alterations were accompanied by a clinical improvement of schizophrenic symptoms. Comparison with healthy controls (n = 30) showed that grey matter amount in the respective amygdalar region was significantly reduced in unmedicated first-episode schizophrenia patients. These findings suggest that drug-induced neuroplastic changes in schizophrenia can occur quickly and are dependent on pharmacokinetics

Individuals under voluntary treatment with sexual interest in minors: what risk do they pose?

Child Sexual Abuse (CSA) and the production, use, and distribution of Child Sexual Abuse Material (CSAM) are key threats to children’s mental health. From the perspective of indicated prevention, it can be assumed that some persons with a sexual interest in children commit such unreported crimes. Accordingly, the German Network kein Täter werden (meaning do not offend) has implemented a confidential treatment service for persons with a sexual interest in minors who voluntarily seek therapy, might or might not have offended but have not yet been detected or have fulfilled all legal requirements (here referred to as non-forensic individuals). However, this offer has been questioned for investing resources in a group which critics consider as low risk. The following study addresses the question of recidivism risks for CSA or viewing CSAM among non-forensic individuals. We found significantly higher rates of CSA/CSAM in our participants’ history compared to a German study on a representative sample of males. Regarding CSAM, the recidivism rate of 39% was found to be 11 times higher than the expected recidivism rate based on previous publications. Regarding CSA, the recidivism rate of 14% was not significantly different from the expected rate reported for subjects with a conviction for a sexual contact offense. Among various risk instruments, only the CPORT with CASIC rating was able to predict CSA (AUC = 0.69, 95% CI = 0.55, 0.82) and CSAM (AUC = 0.63, 95% CI = 0.53, 0.73) among individuals with a history of CSAM, but with poor discrimination. We conclude that a large proportion of our sample poses a substantial risk and therefore treatment resources are well invested. However, further studies are needed to improve risk assessment among non-forensic clients

Paired Associative Stimulation of the Auditory System: A Proof-Of-Principle Study

Background Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS. Methods Acoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design. Results Amplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone. Conclusion These findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity

Transcranial Magnetic Stimulation for the treatment of tinnitus: Effects on cortical excitability

<p>Abstract</p> <p>Background</p> <p>Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positron-emission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single- and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitus-questionnaire.</p> <p>Results</p> <p>We noted a significant interaction between treatment response and changes in motor cortex excitability during active rTMS. Specifically, clinical improvement was associated with an increase in intracortical inhibition, intracortical facilitation and a prolongation of the cortical silent period. These results indicate that intraindividual changes in cortical excitability may serve as a correlate of response to rTMS treatment.</p> <p>Conclusion</p> <p>The observed alterations of cortical excitability suggest that low frequency rTMS may evoke long-term-depression like effects resulting in an improvement of subcortical inhibitory function.</p