Case report: Hyperactive delirium after a single dose of zolpidem administered additionally to psychopharmacotherapy including clozapine.

The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics. The present case report portrays a young male Caucasian inpatient with schizoaffective disorder, who was admitted due to severe hyperactive delirium after a single dose of zolpidem 10 mg that was administered in addition to already established psychopharmacotherapy including clozapine 200 mg/day, aripiprazole 15 mg/day and cariprazine 4.5 mg/day. In detail, disorientation, agitation, confabulations, bizarre behavior, and anterograde amnesia occurred shortly after ingestion of zolpidem and gained in intensity within a couple of hours. Once zolpidem was discontinued, the abovementioned symptoms subsided completely and did not reoccur. Since a clear temporal association could be drawn between the intake of zolpidem and the onset of hyperactive delirium, the present clinical experience should serve as a cautionary note for combining potent sedative-hypnotics and substances with anticholinergic properties, even in young adults in a good general condition. Moreover, our case argues for the necessity of further research into the pathomechanism of the interaction potential of non-benzodiazepines as zolpidem, especially with substances exerting anticholinergic properties, which are known for their potential to precipitate delirium. Therefore, the metabolic pathways of the concurrently administered substances should be further taken into account.

Intravenous esketamine leads to an increase in impulsive and suicidal behaviour in a patient with recurrent major depression and borderline personality disorder.

Objectives: As clinical studies demonstrated that ketamine possesses rapid-acting antidepressant and antisuicidal effects, it is increasingly used in affective disorders. The neuroplastic properties of ketamine are well described in preclinical and imaging studies, and are highly related to its antidepressive mechanism of action.Methods: Here, we report on a female patient with recurrent major depression and borderline personality disorder (BPD) who was treated with intravenous (i.v.) esketamine as rapid-acting augmentation therapy to improve severe and acute depressive symptoms and suicidal behaviour.Results: Esketamine led to an initial improvement of these symptoms. However, during the course of treatment, loosened and disinhibited behaviour and severe suicidal ideation occurred during and immediately after esketamine application. Hence, i.v. esketamine was discontinued, and she further received treatment as usual, which demonstrated to be beneficial.Conclusions: With current knowledge at hand, one cannot exclude esketamine's effects on the equilibrium of neural plasticity in brain networks, potentially initiating undesirable symptoms as impulsive behaviour and emotional dysregulation. Therefore, until investigations focus on efficacy and side effects profile of esketamine in depressed patients with (comorbid) BPD, treatment with this fast-acting medication should be considered with caution in this patient group.

Proposed Indoor Test Procedure to Quantify Pesticide Treatment Effects on Seed Consumption by Birds.

Pesticides used in seed coatings can influence seed consumption by birds and, therefore, actual exposure risk for them. A quantification of such effects on consumption is currently not regarded as a refinement factor in environmental risk assessments, although it is a possible option and should be considered, for example, for comparing exposure risk of different pesticides. It can highlight avoidance behavior, preventing birds from taking up lethal or sublethal pesticide doses. To formulate a standard, we developed an indoor test procedure based on established pen test methods, including 2- and no-choice phases with hunger periods. During testing, the highest standards of animal welfare were applied. Statistical approaches were used to determine the most appropriate number of replicates and for analysis. The effect on consumption of seeds is expressed as the ratio of consumed treated to untreated seeds. This consumption factor can be applied in avian risk assessments for seed treatments equivalent to an avoidance factor. We present, as an example, an application of the procedure to obtain a seed- and species-specific consumption factor for oilseed rape seeds (Brassica napus) provided untreated and treated with fungicides to greenfinches (Carduelis chloris) and Japanese quail (Coturnix japonica). Overall, bird constitution was not negatively affected by the test procedure in either species. The test procedure was suitable for showing differences in expected consumption patterns, such as greater avoidance of treated seeds in 2-choice than in no-choice tests. However, the consumption differed between species and fungicide treatments, allowing us to rank avoidance effects of different fungicides. Using the presented standard procedure to generate comparable pesticide- and species-specific consumption factors for more species and seed treatments may result in refinement of default values and reduce animal trials in different designs in the future. Environ Toxicol Chem 2020;39:359-370. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases.

Ketamine, a rapid-acting antidepressant and anti-suicidal agent, is thought to increase brain monoamine levels by enhancing monoamine release or inhibiting presynaptic monoamine-reuptake. Here we present two female inpatients suffering from treatment-resistant depression with recurrent severe suicidal crises receiving a combination of intravenous S-ketamine and oral tranylcypromine, which is a well-known irreversible monoamine oxidase (MAO) inhibitor. Since inhibition of monoamine-reuptake with concurrent blockade of MAO might trigger sympathomimetic crisis, this combination is considered hazardous. Nonetheless, cardiovascular parameters remained stable in both patients, while good anti-suicidal effects were observed. Hence, we put serious doubt on whether monoamine-reuptake inhibition is a relevant pharmacological effect of ketamine in humans.

Actigraphic measurements in opioid detoxification with methadone or buprenorphine.

The objective of the present naturalistic study was to assess the differential effects of opioid detoxification with methadone or buprenorphine on activity, circadian rhythm, and sleep. Forty-two consecutive inpatients with opiate addiction were switched to either methadone or buprenorphine and gradually tapered down over the course of 2 to 3 weeks. There were no significant differences in comedication (lofexidine, quetiapine, and valproic acid) between the methadone and buprenorphine groups. Patients in the methadone group showed 11% lower activity and were 24 minutes phase delayed as compared with buprenorphine-treated patients, whereas the latter had 2.5% lower sleep efficiency and 9% shorter actual sleep time. These significant group differences were most pronounced for the lowest doses (≤20% of maximum individual daily dose, ie, at the end of withdrawal representing late withdrawal effects). Furthermore, for the total sample, we found a significant decrease in the relative amplitude of the sleep-wake cycle and worsening of all actigraphic sleep parameters from the higher (100% to 20%) to the lowest doses (20% to 0%). The acrophase of the circadian rhythm displayed a phase advance (-88 minutes) from the highest (100% to 80%) to the lower doses (80% to 0%) in methadone-treated patients. Opioid tapering with methadone or buprenorphine leads to characteristic changes of the rest-activity cycle, but further study is required to validate these results.

Self-poisonings with tricyclic antidepressants and selective serotonin reuptake inhibitors in Tehran, Iran.

In a prospective hospital-based cohort study, we addressed the question of severity and outcome of antidepressant poisonings in patients who attended the Loghman-Hakim Hospital Poison Center, the only national center in Tehran dedicated for detoxification. The aim of the study was to find out if tricyclic antidepressant (TCA) intoxications require more therapeutic efforts than selective serotonin reuptake inhibitor (SSRI) intoxications. The study was applied over a 7-week period (28 March-20 May 2006). From 3578 intoxications, 334 patients with antidepressant or lithium self-poisoning were identified (9.3% of all poisoning cases; 233 females, 101 males; median age 24 years, min 13, max 70). Compared to SSRI single-substance intoxications (n=17), TCA single-substance intoxications (n=73) were associated with: (1) a significantly lower level of consciousness (P=0.005); (2) a significantly higher admission frequency (80.8 vs. 35.3%; P<0.001); and (3) a higher intubation frequency (13.7 vs. 0%; P=ns). SSRI multiple-substance intoxications were associated with a significantly lower level of consciousness than SSRI single-substance intoxications (P=0.042), while there was no significant difference between TCA multiple- and single-substance intoxications. This study suggests that an overdose with SSRIs results in a more favourable clinical outcome than an overdose with TCAs.

Validation of a simplified definition of anger attacks.

BACKGROUND: Anger attacks, sudden spells of anger with vegetative hyperarousal, are highly prevalent symptoms in depression. Assessment normally requires the use of specific instruments. The aim of this study was the validation of a simplified definition for anger attacks. METHODS: Anger attacks were assessed in 203 patients suffering from major depression with the Anger Attacks Questionnaire. The first three items of the questionnaire (irritability, overreaction to minor annoyances, episodes with inappropriate anger or rage) were compared separately with the diagnosis, and their value as single screening questions to establish the diagnosis was assessed. RESULTS: Irritability was only weakly associated with the diagnosis of anger attacks (Cohen's kappa kappa = 0.214 +/- 0.058) and yielded a rather low specificity (0.302), while overreaction to minor annoyances (kappa = 0.869 +/- 0.037) and the question about episodes with inappropriate anger or rage (kappa = 0.901 +/- 0.032) had a high degree of agreement with the diagnosis of the questionnaire (specificity 0.918 and 0.935, respectively). The combination of the two later items resulted in an almost perfect reclassification of cases (kappa = 0.955 +/- 0.022; specificity = 0.971). CONCLUSIONS: As anger attacks are probably underdiagnosed in clinical practice, simplification of the diagnostic process is imperative. Our results demonstrate that asking one or two simple screening questions suffices to recognize the majority of patients with anger attacks.

Effect of intravenous magnesium sulphate in reducing irritability and restlessness in pure and polysubstance opiate detoxification.

The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of intravenous magnesium sulphate (MgSO(4)) on the need for chlormethiazole in pure or polysubstance opiate detoxification. Forty-one inpatients suffering from pure and polysubstance opiate dependence were treated with morphine sulphate pentahydrate in a gradual detoxification program. Morphine reduction took about 11 days. Additionally, 5% MgSO(4) was administered intravenously to the intervention group (Mg group, n=22) over 24 h by perfusor (150-200 mg MgSO(4)/h; plasma level of 2.36+/-0.29 mmol/l), whereas NaCl 0.9% was intravenously administered in the placebo group (n=19). In case of withdrawal symptoms (irritability, restlessness, and insomnia), patients received chlormethiazole p.o. Our hypothesis that the need for chlormethiazole would be decreased by adjunctive administration of Mg was not confirmed in our study population (2180 mg/day in the Mg group vs. 2360 mg/day in the placebo group). There was neither a difference in the quantity of chlormethiazole required nor a difference in the severity of withdrawal symptoms measured with the Wang scale between the two comparison groups. We observed that calcium plasma levels decreased and phosphate plasma levels increased significantly during intravenous therapy with Mg. Despite promising pilot studies, the administration of Mg did not enable a dose reduction of tranquilizing medication (chlormethiazole) in pure and polysubstance opiate detoxification.

White matter hyperintensities and chronicity of depression.

OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic resonance imaging (MRI) of the brain are associated with advanced age and late-life depression. Most investigations predominantly found these lesions in frontal lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction in depression. A prospective study was undertaken to investigate the association between extent of WMHs and clinical outcome in elderly depressed patients. METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI scan. The MRI scans were analysed in consensus by two experienced radiologists. Each MRI scan was assessed for presence and extent of WMHs, which are differentiated in periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31 patients were re-assessed 5 years after baseline assessment. We ascertained the severity of depressive symptoms, the longitudinal course of depression, the cognitive decline and the global assessment of functioning at follow-up visit. RESULTS: (1) Subjects with greater extent of WMHs had a significant higher Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal courses of depression (3) and had a lower Mini-Mental State Examination (MMSE) score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly depressed subjects. Further studies are needed to evaluate WHMs as prognostic factor for an appropriate treatment decision-making.

Seasonality of birth in seasonal affective disorder.

BACKGROUND: Season of birth or seasonal changes in putative etiologic factors are thought to influence the development of several psychiatric illnesses. The aim of this investigation was to examine seasonal differences in the frequency of birth in a clinical sample of patients with seasonal affective disorder (SAD). METHOD: 553 outpatients suffering from SAD-DSM-IV-defined depressive disorder with winter-type seasonal pattern-who had been diagnosed and treated at the Department of General Psychiatry (University of Vienna, Austria) between 1994 and 2003, were included in this evaluation. We compared the observed number of births in our sample with expected values calculated from the general population. RESULTS: There was a significant deviation of the observed number of births from the expected values calculated on a monthly basis (p = .009). When comparing quarters (periods of 3 months), we found fewer births than expected in the first quarter of the year and a slight excess of births in the second and third quarters (p = .034). There were also more births in the spring/summer season and fewer than expected in fall and winter (p = .029). Interestingly, patients with melancholic depression were more frequently born in fall/winter and less often in spring/summer compared with patients with atypical depression (p = .008). CONCLUSION: Besides genetic factors, season of birth or seasonal changes in environmental factors also could influence the development of SAD. In addition, birth effects seem to be dependent on the symptom profile of the patients, but further studies are needed to elucidate the underlying mechanisms of these observations.

Gender differences in the psychopathology of depressed inpatients.

In the last few years there has been increased scientific effort to describe the gender-specific psychopathological features of depression. Until now these studies have not been entirely conclusive, which could be the result of methodological difficulties. This report investigates sex differences in the symptom presentation in an inpatient population: 104 female and 113 male patients suffering from a depressive episode according to ICD-10 were admitted to the inpatient treatment at the Department of General Psychiatry in Vienna. A psychopathological rating according to the standardized documentation system of the AMDP (Association for Methodology and Documentation in Psychiatry) was performed at admission and discharge. At admission into the hospital women tended to show more affective lability (p = 0.025), whereas men had higher scores in affective rigidity (p = 0.032), blunted affect (p = 0.002), decreased libido (p = 0.028), hypochondriasis (p = 0.016) and hypochondriac delusions (p = 0.039). At discharge from the hospital women had significantly higher scores in dysphoria (p = 0.010), while men were more prone to have compulsive impulses (p = 0.030). Although our results were obtained in a selected sample of inpatients at a university hospital, they are indicative of psychopathological differences between men and women in the core symptoms of depression. These differences may influence diagnostic practice and gender specific treatment of depression.

Bright light therapy in seasonal affective disorder--does it suffice?

Bright light therapy (BLT) has been proposed as treatment of choice for seasonal affective disorder (SAD). However, conventional antidepressants have also been found to be effective in this condition. We examined the psychopharmacologic medication in a clinical sample of 553 SAD patients, who had been treated with BLT, to assess the importance of drug treatment and to critically question the effectiveness of BLT. Forty-nine percent of our patients received psychopharmacologic treatment and about one third (35.4%) was treated with antidepressants, suggesting that BLT does not suffice as only antidepressant regimen for all SAD patients. Furthermore, our results show that only few patients with bipolar affective disorder were willing to accept long-term medication. Opposed to treatment guidelines, patients with several depressive episodes did not receive antidepressant maintenance medication or mood stabilizers more often than patients with only a few episodes.

Possible linkage of schizophrenia and bipolar affective disorder to chromosome 3q29; a follow-up.

The present linkage study is a follow-up within the chromosome 3q29 region in schizophrenia and bipolar affective disorder families, based on our recently published genome scan, resulting in evidence for linkage of both disorders to this region (marker D3S1265: NPL [non parametric lod] score Z(all)=3.74, P=0.003). Using the same family sample (five pedigrees with schizophrenic index patients and three pedigrees with index bipolar disorder patients N=86; 50 of them were available for genotyping), genotyping of eight additional markers close to D3S1265 was done. Five of those new markers (three centromeric and two telomeric of D3S1265) spanning 4.14 cM (centiMorgan) could be used for statistical analyses ("new markers"). Moreover, marker D3S1265, genotyped within the published genome scan, was used for additional calculations. Linkage analysis was performed using the GENEHUNTER program version 2.1r3. Within newly genotyped markers the highest NPL score Z(all) observed was 1.93296 with the telomeric SNP (single nucleotide polymorphism) rs1835669, corresponding to P=0.032166. Statistical analysis including D3S1265, located in between the newly genotyped markers, resulted in a peak NPL score Z(all)=4.00179 with marker D3S1265, that is P=0.000128. Doing subset analyses of the bipolar disorder and schizophrenia families separately with new markers and D3S1265, linkage signals arose substantially from bipolar disorder families, with contribution from schizophrenia families, too. The results of our follow-up study support our previous linkage finding of schizophrenia and bipolar affective disorder to chromosome 3q29.

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

RATIONALE AND OBJECTIVES: This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. METHODS: Short-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. RESULTS: Metabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. CONCLUSIONS: The authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

[Transcranial magnetic stimulation (TMS)--from diagnostic procedure to therapy]. / Transkranielle Magnetstimulation (TMS)--vom diagnostischen Verfahren zur Therapie.

Transcranial magnetic stimulation (TMS) has been a well-established diagnostic tool in neurological practice for many years. It has been shown to be a safe and well tolerated method. Lately this technique has also found its way to psychiatry for the treatment of mood disorders. Several studies which investigated TMS of deeper brain regions found antidepressive effects in analogy to electro convulsive therapy (ECT). This could present a significant advantage, because TMS provides non-invasive and painless stimulation of the cerebral cortex. The method is based on the principle that a time-varying magnetic field induces an electric field which leads to activation of inhibitory and excitatory neurons in neural tissue. The magnetic field pervades the intact scalp and skull without loss of energy. Both case reports as well as clinical studies have shown that TMS could present a promising option in the treatment of depression. A review of the literature demonstrates that further studies are needed to clarify many questions regarding technical and clinical aspects, such as dosage, duration of application, localization of the coils, as well as the impact of rapid-rate TMS and stronger magnetic field generators, before TMS will become an established tool in the treatment of psychiatric disorders.

Maternal bonding behaviour in schizophrenia and schizoaffective disorder, considering premorbid personality traits.

OBJECTIVE: Bonding between mother and child is described as a complex two-way process ensuring the needs of the child for nurture and protection. As such, it is dependent on the contribution of mother and child [1-3] whereby characteristics of personality of the child may have consequences on maternal bonding behaviour. In the current study the perception of maternal behaviour, premorbid personality traits and relationships between maternal behaviour and personality traits were investigated in schizophrenic and schizoaffective patients and their same-sex, healthy siblings. METHODS: We recruited 36 schizophrenic and schizoaffective patients and their same-sex healthy siblings. Information about maternal bonding behaviour was assessed by the Parental Bonding Instrument, information about premorbid personality traits was obtained from their mothers using the "Giessen-Test". RESULTS: Compared to their siblings, patients showed less social resonance, more permeability, less social competence and a more depressed and anxious mood. Furthermore, patients described their mothers to be less caring and to be more overprotective than their siblings described them. But there were strong associations between maternal bonding behaviour and premorbid personality traits. These findings were supported by missing significant differences in maternal care behaviour between patients and siblings when using premorbid characteristics as covariates. Significant high maternal overprotection perceived by patients with schizophrenia and schizoaffective disorders still remained after correcting for the influence of premorbid personality traits. CONCLUSION: The results suggest that premorbid personality traits should be considered not only in analyses of maternal care behaviour in schizophrenic and schizoaffective patients but also when studying other psychiatric patient groups.

Genome scan for susceptibility loci for schizophrenia and bipolar disorder.

BACKGROUND: Despite the widely accepted view that schizophrenia and bipolar disorder represent independent illnesses and modes of inheritance, some data in the literature suggest that the diseases may share some genetic susceptibility. The objective of our analyses was to search for vulnerability loci for the two disorders. METHODS: A genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Linkage analyses was used to compute the usual parametric logarithm of the likelihood of linkage (LOD) scores and nonparametric linkage analysis (NPL scores Z(all)) was used to assess the pattern of allele sharing at each marker locus relative to the presence of the disease (GENEHUNTER). Affected status was defined as severe affective disorder or schizophrenia. RESULTS: Across the genome, p values associated with NPL scores resulted in evidence (i.e., p <.0007) for linkage at marker D3S1265 on chromosome 3q (NPL score Z (all) = 3.74, p =.0003). Two other markers (on 3q and 6q) showed p values of <.01. CONCLUSIONS: We detected a potential susceptibility locus for bipolar disorder and schizophrenia on chromosome 3q, which has not been reported previously. The possibility of a false positive result has to be taken into account. Our data suggest shared loci for schizophrenia and bipolar affective disorders and are consistent with the continuum model of psychosis.