Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study.

Despite many pharmacological and psychosocial treatment options, schizophrenia remains a debilitating disorder. Thus, new treatment strategies rooted in the pathophysiology of the disorder are needed. Recently, vagus nerve stimulation (VNS) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia. The objective of this study was to investigate for the first time the feasibility, safety and efficacy of transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham-controlled, double-blind trial was conducted from 2010 to 2012. Twenty schizophrenia patients were randomly assigned to one of two treatment groups. The first group (active tVNS) received daily active stimulation of the left auricle for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation. Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12. Various other secondary measures were assessed to investigate safety and efficacy. The intervention was well tolerated with no relevant adverse effects. We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period. Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups. Application of tVNS was well tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia, the overall pattern of symptom change might warrant further investigations in this population.

[Pregnant opioid addicted patients and additional drug intake. Part II: Comorbidity and their therapy]. / Therapie von schwangeren Patientinnen mit Abhängigkeit von Opioiden und begleitenden Suchtstoffen. Teil II: Therapie der Komorbiditäten.

The majority of opioid dependent patients suffer from various psychiatric and somatic comorbid diseases like mood and anxiety disorders, psychotic diseases, personality disorders, HIV infection, Hepatitis B and C. If medical treatment is needed, grouping active substances to FDA Pregnancy Categories (A, B, C, D or X) may be helpful. The majority of substances reported here only fulfill the FDA-categories C or D, which means that they could have teratogenic effects, but with probably different rank order. First of all, referring to mood, personality and anxiety disorders, the focus should be laid on non-pharmacological treatment by offering psychotherapeutic and supporting psychosocial interventions to the patients. However, opioid dependent pregnant patients who suffer from severe diseases such as psychosis, bipolar affective disorder or severe depression, may need psychoactive medication like antipsychotics, antidepressants or mood stabilizers to prevent them from harm caused by psychotic ideas and actions and/or suicidality. However these medications may comprise fetal risks, especially when taken together, and therefore should only be used when benefit and risks are considered together with patients and their relatives. It is important to avoid acute or renewed psychiatric decompensation. We present the current differentiated knowledge for therapy of opioid dependent patients with antipsychotics, antidepressants (e.g. higher fetal risk in case of treatment with fluoxetine and paroxetine) or mood stabilizers. All of them should only be used after considering benefit and risks. During pregnancy, there should not be switched between different antidepressant drugs. Referring mood stabilizers, the intake of valproic acid should be avoided in pregnancy or at least, dosage should be kept as low as possible since severe teratogenetic effects are known. In addition the specific drug treatment of HIV and hepatitis B during pregnancy is described. During childbirth HIV-infected patients should receive zidovudine intravenously to prevent vertical transmission. Co-infection with hepatitis C cannot be treated during pregnancy, since interferons are associated with a severe risk of fetal malformations and ribavirin has teratogenic effects; for this reason interferon therapy should be started after delivery.

[Pregnant opioid addicted patients and additional drug intake. Part I. Toxic effects and therapeutic consequences]. / Therapie von schwangeren Patientinnen mit Abhängigkeit von Opioiden und begleitenden Suchtstoffen. Teil I: Toxische Folgen und therapeutische Konsequenzen.

Opioid dependent patients often are dependent from the illegal consumption of heroin and, in addition, perform a polytoxicomanic way of consuming drugs. They suffer of various somatic and psychiatric diseases. Moreover, pregnancies of drug addicted women are classified as high-risk pregnancies. With respect to the particular consumed drug substances other than opioids during pregnancy variable forms of teratogenic and toxic effects can be assigned to the baby. Critical values of maternal substance abuse referring to fetal impairment do not exist. With regard to the possible teratogenic and toxic fetal effects of maternal consume of alcohol, tobacco, sedativa, cannabis, cocaine and amphetamines, withdrawal treatment of polytoxicomanic pregnant patients under inpatient medical supervision including medication if necessary represent the first-line-treatment. With respect to smoking, it is possible to detoxicate the patients also by an outpatient treatment. However, referring to heroin addiction, a maintenance therapy with L-methadone, D/L-methadone or buprenorphine should be preferred since fetal withdrawal symptoms of opioids otherwise can cause severe complications which even can lead to the loss of the fetus and also increase the risks for the mother. Increasing the dose of the opioid substitute may be necessary, for example, to avoid premature uterus contractions. It is to be pointed out that substitution treatment with methadone or buprenorphine also improve the medicinal compliance and psychosocial circumstances of the pregnant patients. Subsequent to delivery, the maintenance treatment should initially be pursued over a further period of time. In the follow up, the question of continuing with maintenance treatment or starting a withdrawal treatment of opioids should be discussed on an individual basis. To sum up, proceeded interdisciplinary care during pregnancy and afterwards by all the professions involved like general practioners as well as social workers, gynaecologists, paediatrists, pharmacists, psychologists and psychiatrists should be ensured. Futhermore, diagnosis and therapy of the comorbid psychiatric and infectious diseases like hepatitis A, B, C and HIV are necessary and described (see Part II. Comorbidity and their treatment).

Anxiety- and novelty seeking-related personality traits and serotonin transporter gene polymorphisms.

The affection of human personality by the promoter and the intron 2 polymorphism in the serotonin transporter gene (SERT) is inconsistently reported. We aimed to clarify this situation by gender-specific haplotype-phenotype association. 98 women and 97 men completed the personality inventories NEO-PI-R and TPQ. The subjects were genotyped for the two SERT polymorphisms and the haplotypes were calculated. The short (S) and long (L) promoter alleles and the 12 and 10 repeat intron 2 alleles formed the haplotypes S 12, S 10, L 12 and L 10. In men, scores in the anxiety-related dimensions were higher in S 12 than in L 12 carriers. Opposite in direction, scores tended to be lower in S 10 than in L 10 carriers. In the novelty seeking-related dimensions, scores were higher in S 10 than in S 12 carriers. No association was observed in women. In conclusion, anxiety- and novelty seeking-related personality dimensions are differentially associated with different SERT haplotypes; the consistent restriction to men suggests common androgen regulation. Opposite trends with haplotypes including the same promoter alleles suggest contribution of group stratification to earlier inconsistent findings and call to further differentiate the molecular function and clinical implications of the SERT promoter polymorphism.