Stefanie Jung

Agitation Predicts Response of Depression to Botulinum Toxin Treatment in a Randomized Controlled Trial

In a randomized, controlled trial (n = 30), we showed that botulinum toxin injection to the glabellar region produces a marked improvement in the symptoms of major depression. We hypothesized that the mood-lifting effect was mediated by facial feedback mechanisms. Here we assessed if agitation, which may be associated with increased dynamic psychomotor activity of the facial musculature, can predict response to the treatment. To test this hypothesis, we re-analyzed the data of the scales from our previous study on a single item basis and compared the baseline scores in the agitation item (item 9) of the Hamilton Depression Rating Scale (HAM-D) between responders (n = 9) and participants who did not attain response (n = 6) among the recipients of onabotulinumtoxinA (n = 15). Responders had significantly higher item 9 scores at baseline [1.56 + 0.88 vs. 0.33 + 0.52, t(13) = 3.04, d = 1.7, p = 0.01], while no other single item of the HAM-D or the Beck Depression Inventory was associated with treatment response. The agitation score had an overall precision of 78% in predicting response in a receiver operating characteristic (ROC) analysis (area under the curve, AUC = 0.87). These data provide a link between response to botulinum toxin treatment with a psychomotor manifestation of depression and thereby indirect support of the proposed facial feedback mechanism of action. Moreover, it suggests that patients with agitated depression may particularly benefit from botulinum toxin treatment.

Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials.

INTRODUCTION Botulinum toxin A (BTA) injection into the glabellar region is currently being studied as a treatment for major depressive disorder (MDD). Here we explore efficacy data of this novel approach in a pooled analysis. METHODS A literature search revealed 3 RCTs on this topic. Individual patient data and clinical end points shared by these 3 trials were pooled and analyzed as one study (n=134) using multiple regression models with random effects. RESULTS In the pooled sample, the BTA (n=59) and the placebo group (n=75) did not differ in the baseline variables. Efficacy outcomes revealed BTA superiority over placebo: Improvement in the Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale 6 weeks after baseline was 45.7% for BTA vs. 14.6% for placebo (p<0.0001), corresponding to a BTA response rate of 54.2% (vs. 10.7%) and a BTA remission rate of 30.5% (vs. 6.7%). DISCUSSION Equalling the status of a meta-analysis, this study increases evidence that a single treatment of BTA into the glabellar region can reduce symptoms of MDD. Further studies are needed to better understand how BTA exerts its mood-lifting effect.

Inhaled Loxapine for Acute Treatment of Agitation in Patients With Borderline Personality Disorder: A Case Series.

To the Editors: A cute agitation is very common in patients with borderline personality disorder (BPD). A novel approach for short-term treatment of acute agitation in schizophrenia and bipolar disorder is loxapine as inhalation (Adasuve; Staccato System), which has been approved in the United States since December 2012 and in the European Union since February 2013. Efficacy may also be expected for states of agitation in other psychiatric diseases such as BPD. Loxapine is a tricyclic antipsychotic with a tmax median of 2 minutes after inhalation and a mean half-life of 6.2 hours. The delivery

Lack of Increase in Sexual Drive and Function After Dopaminergic Stimulation in Women

ABSTRACT Human and animal data indicate that the dopaminergic system plays a crucial role in sexual drive and function. Using a double-blind, placebo-controlled crossover design, this prototype study investigated the effect of the D2 dopamine agonist cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital parameters were monitored continuously. Sexual drive and function were measured using self-report sexual experience scales. In contrast to previous theories and assumptions, we found that cabergoline did not alter objective and subjective sexual parameters in healthy women. This finding suggests that there may be sex differences in the influence of the dopaminergic system on human sexual functioning.

[Inhaled loxapine for emergency treatment of agitated patients with borderline personality disorder : A series of five cases].

Patienten mit Borderline-Persönlichkeitsstörung (BPS) leiden häufig an den Symptomen einer Agitation wie Unruhe, Erregung und inneren Spannungen. Diese können in schwere Autoaggression und selbstverletzendes Verhalten eskalieren, mit dem die Betroffenen versuchen, die für sie unerträgliche innere Anspannung zu lösen. Wenn psychotherapeutische Deeskalationsmethoden versagen, empfehlen nationale und internationale Leitlinien und Konsenserklärungen den Einsatz nichtsedierender, nichtinvasiver Medikamente mit schnellem Wirkungseintritt und einem günstigen Nebenwirkungsprofil [2, 5, 11, 15, 23]. Derzeit zählen Benzodiazepine, orale und injizierbare Antipsychotika zur Standardbehandlung akut agitierter Patienten. Die genannten Therapieoptionen können im Kontext einer BPS Nachteile haben: Neben dem Risiko einer Sedation und Abhängigkeitsentwicklung sind unterderTherapiemitBenzodiazepinenbei bis zu 50%der Patienten paradoxe Reaktionen beschrieben worden [18], zudem wurde unter der Gabe von Alprazolam eine Abnahme der Verhaltenskontrolle bei BPS beobachtet [6]. Orale Antipsychotika haben oft einen verzögerten Wirkungseintritt, während die Gabe intramuskulär injizierter Antipsychotika selbst unter günstigsten Voraussetzungen nicht als „nichtinvasives“ Verfahren aufgefasst werden kann [1, 17]. Zusammengefasst ist die Therapie der akuten Agitation bei BPS arbiträr, es fehlen randomisiert-kontrollierte Studien, und kein Medikament ist für die medikamentöse Therapie der BPS zugelassen. Bei agitierten erwachsenen Patienten mit Schizophrenie oder bipolarer Störung steht dagegen in Deutschland seit Februar 2013 mit inhalativem Loxapin eine neue Behandlungsoption zur Verfügung [8]. Aufgrund der Applikationsart weist inhalatives Loxapin eine schnelle Bioverfügbarkeit und einen raschen Wirkeintritt von < 10 min auf [3, 10]. Eine relevante Nebenwirkung ist symptomatischer Bronchospasmus, der häufiger bei Patienten mit vorbestehendem Asthma bronchiale (53,8 % Bronchospasmus vs. 11,5 % nach Placebogabe) und chronisch-obstruktiver Lungenerkrankung (23,1 % vs. 14,8 % nach Placebogabe) auftritt [7]. Unter Beachtung dieser Nebenwirkungen bei entsprechend vorerkrankten Patienten könnte sich inhalatives Loxapin auch als Notfallmedikation für agitierte Patienten mit BPS eignen, um nachfolgende Selbstverletzungen und damit verbundene Komplikationen zu vermeiden.

Inhalatives Loxapin zur Notfallbehandlung bei agitierten Patienten mit Borderline-Persönlichkeitsstörung

Patienten mit Borderline-Persönlichkeitsstörung (BPS) leiden häufig an den Symptomen einer Agitation wie Unruhe, Erregung und inneren Spannungen. Diese können in schwere Autoaggression und selbstverletzendes Verhalten eskalieren, mit dem die Betroffenen versuchen, die für sie unerträgliche innere Anspannung zu lösen. Wenn psychotherapeutische Deeskalationsmethoden versagen, empfehlen nationale und internationale Leitlinien und Konsenserklärungen den Einsatz nichtsedierender, nichtinvasiver Medikamente mit schnellem Wirkungseintritt und einem günstigen Nebenwirkungsprofil [2, 5, 11, 15, 23]. Derzeit zählen Benzodiazepine, orale und injizierbare Antipsychotika zur Standardbehandlung akut agitierter Patienten. Die genannten Therapieoptionen können im Kontext einer BPS Nachteile haben: Neben dem Risiko einer Sedation und Abhängigkeitsentwicklung sind unterderTherapiemitBenzodiazepinenbei bis zu 50%der Patienten paradoxe Reaktionen beschrieben worden [18], zudem wurde unter der Gabe von Alprazolam eine Abnahme der Verhaltenskontrolle bei BPS beobachtet [6]. Orale Antipsychotika haben oft einen verzögerten Wirkungseintritt, während die Gabe intramuskulär injizierter Antipsychotika selbst unter günstigsten Voraussetzungen nicht als „nichtinvasives“ Verfahren aufgefasst werden kann [1, 17]. Zusammengefasst ist die Therapie der akuten Agitation bei BPS arbiträr, es fehlen randomisiert-kontrollierte Studien, und kein Medikament ist für die medikamentöse Therapie der BPS zugelassen. Bei agitierten erwachsenen Patienten mit Schizophrenie oder bipolarer Störung steht dagegen in Deutschland seit Februar 2013 mit inhalativem Loxapin eine neue Behandlungsoption zur Verfügung [8]. Aufgrund der Applikationsart weist inhalatives Loxapin eine schnelle Bioverfügbarkeit und einen raschen Wirkeintritt von < 10 min auf [3, 10]. Eine relevante Nebenwirkung ist symptomatischer Bronchospasmus, der häufiger bei Patienten mit vorbestehendem Asthma bronchiale (53,8 % Bronchospasmus vs. 11,5 % nach Placebogabe) und chronisch-obstruktiver Lungenerkrankung (23,1 % vs. 14,8 % nach Placebogabe) auftritt [7]. Unter Beachtung dieser Nebenwirkungen bei entsprechend vorerkrankten Patienten könnte sich inhalatives Loxapin auch als Notfallmedikation für agitierte Patienten mit BPS eignen, um nachfolgende Selbstverletzungen und damit verbundene Komplikationen zu vermeiden.

The New Hamburg-Hannover Agitation Scale in Clinical Samples: Manifestation and Differences of Agitation in Depression, Anxiety, and Borderline Personality Disorder

Background/Aims: Agitation is a burdening phenomenon that occurs in a variety of psychiatric disorders. The aim of this study was to give a first direction for agitation occurrence in depression, anxiety disorder, and borderline personality disorder (BPD) as well as in healthy controls with and without psychiatric record. Methods: Using the Hamburg-Hannover Agitation Scale (H2A), an instrument that allows for the measurement of agitation independently of the presence of a specific disorder, a patient sample (n = 158) and a healthy control group (n = 685) with (n = 94) and without (n = 591) psychiatric record were examined. The data were mainly analysed using ANOVAs and post hoc tests. Results: Patients showed significantly higher H2A agitation levels than healthy controls. Within the clinical sample, BPD patients exhibited the strongest manifestation of agitation, scoring significantly higher than the depression and the anxiety disorder sample, while these two subgroups did not significantly differ from each other. Moreover, healthy subjects with a psychiatric record experienced a significantly stronger agitation than subjects without a psychiatric record. Conclusion: Further studies are needed with larger, more balanced, and differentiated sample sizes including a wider range of clinical pictures. The results demonstrate that agitation occurs and differs in psychiatric patients as well as in healthy controls.

Clinical characteristics associated with paedophilia and child sex offending – Differentiating sexual preference from offence status

Contrary to public perception, child sex offending (CSO) and paedophilia are not the same. Only half of all cases of CSO are motivated by paedophilic preference, and a paedophilic preference does not necessarily lead to CSO. However, studies that investigated clinical factors accompanying and contributing to paedophilia so far mainly relied on paedophiles with a history of CSO. The aim of this study was to distinguish between factors associated with sexual preference (paedophile versus non-paedophile) and offender status (with versus without CSO). Accordingly, a 2 (sexual preference) × 2 (offender status) factorial design was used for a comprehensive clinical assessment of paedophiles with and without a history of CSO (n = 83, n = 79 respectively), child sex offenders without paedophilia (n = 32) and healthy controls (n = 148). Results indicated that psychiatric comorbidities, sexual dysfunctions and adverse childhood experiences were more common among paedophiles and child sex offenders than controls. Offenders and non-offenders differed in age, intelligence, educational level and experience of childhood sexual abuse, whereas paedophiles and non-paedophiles mainly differed in sexual characteristics (e.g., additional paraphilias, onset and current level of sexual activity). Regression analyses were more powerful in segregating offender status than sexual preference (mean classification accuracy: 76% versus 68%). In differentiating between offence- and preference-related factors this study improves clinical understanding of both phenomena and may be used to develop scientifically grounded CSO prevention and treatment programmes. It also highlights that some deviations are not traceable to just one of these two factors, thus raising the issue of the mechanism underlying both phenomena.

Contents Vol. 49, 2016

Founded 1897 as ‘Monatsschrift für Psychiatrie und Neurologie’, continued 1957–1967 as ‘Psychiatria et Neurologia’, continued 1968–1983 as ‘Psychiatria Clinica’ Founders: C. Wernicke and Th. Ziehen Successors: K. Bonhoeffer (1912–1938), J. Klaesi (1939–1967), E. Grünthal (1953–1973), N. Petrilowitsch (1968–1970), Th. Spoerri (1971–1973), P. Berner (1974–1999), E. Gabriel (1974–2004), Ch. Mundt (2000–2011)

Differential Effects of Intranasal Oxytocin Administration On Sexual Functions in Healthy Females: a Laboratory Setting

The neuropeptide oxytocin (OXT) has an impressive variety of physiological functions in maternal and paternal behavior as well as in human sexual behaviors. Based on our previous studies, we hypothesized that OXT should be able to positively influence parameters of sexual function in females. We employed a double-blind, placebo-controlled, crossover design in a laboratory setting involving 27 healthy females (mean±SD: 27.52 ± 8.04). The acute effects of intranasal administered OXT (24 I.U.) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior were analyzed using a psychometric instrument (Acute Sexual Experiences Scale). Additionally we assessed the physiological parameters (e.g. vaginal pulse amplitude, VPA; vaginal blood volume, VBV) using vaginal photoplethysmograph. A confirmatory data analysis, a particularly suitable approach for crossover-design data was chosen for the psychometric parameters. Confirmatory analysis of treatment differences yielded an effect of oxytocin on the ability of having an orgasm in the laboratory ( p > 0.05) as well as on post orgasm contentment ( p > 0.05). Moreover, data indicated a trend concerning the effect of oxytocin on lubrication ( p = 0.085). The physiological parameters (VPA and VBV) showed moderate psychophysiological activation but were not affected by OXT. Our results indicated that intranasal OXT administration in healthy females significantly increased the ability of having orgasm and contentment after orgasm. Women with OXT administration felt easier to have orgasm and more satisfied after sexual intercourse. These findings warrant further investigations, including subjects with sexual and relationship problems.