[Differentiation Between Alzheimer̓s Disease and Old Age Depression: Overview and Conception of a Questionnaire for Relatives]. / Differenzierung zwischen Alzheimer-Demenz und Depression im Alter: Übersicht und Konzeptionierung eines Angehörigen-Fragebogens.

BACKGROUND: Differential diagnosis of Alzheimer's disease and major depression in the elderly is difficult because of overlapping and similar symptoms. A questionnaire for relatives may facilitate the diagnostic burden in clinical practice. MATERIALS AND METHODS: Based on a selection of clinical criteria, an expert survey, and statistical analysis of the expert survey, a questionnaire for relatives was designed. RESULTS: 18 out of 48 suggested clinical criteria were assessed by neuropsychologists as suitable for the differential diagnosis and were summarized in a questionnaire for relatives (ADAD). First results of the validation of the questionnaire gave an indication of the suitability of the clinical criteria. CONCLUSIONS: The ADAD questionnaire could be simply implemented in clinical practice to differentiate between symptoms of Alzheimer's disease and major depression, but it needs to be evaluated in a larger group of patients.

[Effects of lithium, valproic acid, carbamazepine and antipsychotic agents on cognition in bipolar disorders-A systematic review]. / Auswirkungen von Lithium, Valproat, Carbamazepin und Antipsychotika auf die Kognition bei bipolarer Störung ­ ein systematisches Review.

BACKGROUND: Until now the long-term consequences of the medical treatment for bipolar disorder have barely been examined, especially the consequences with respect to cognitive impairment and dementia. Some studies show signs that some treatment options have a better effect on the brain than others. This review summarizes the current state of research. OBJECTIVE: The effects of long-term consequences of lithium, valproic acid, carbamazepine and antipsychotic agents on the development of dementia or cognitive impairments in patients with bipolar disorder were investigated. METHODS: A systematic literature search was carried out in the PubMed data base from May to July 2022. RESULTS: The majority of studies showed that lithium has a neuroprotective effect and can lower the risk of developing dementia, whereas an increased risk was found in patients taking valproic acid. There are only very few studies that deal with antipsychotic medication and the long-term consequences concerning dementia. CONCLUSION: Lithium should be recommended for the long-term treatment of bipolar disorder. Valproic acid should not or carefully be used as it can affect the risk of developing dementia. With respect to antipsychotics there is no recommendation as more studies are needed to evaluate the long-term consequences.

Alzheimer's Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review.

IMPORTANCE: Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear. OBJECTIVE: To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy. METHODS: The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020. RESULTS: Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on Gingko biloba in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research. CONCLUSION: Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.

Psychiatric comorbidities in cancer patients: acute interventions by the psychiatric consultation liaison service.

AIM: The aim of this study was to explore the psychiatric comorbidities in cancer patients examined by the psychiatric consultation liaison services (CLP) in a general hospital. Furthermore, we intended to examine associations between certain cancers types and psychiatric disorders as well as to give an overview of the psychiatric treatments options that were recommended by the CLP. METHODS: This retrospective analysis investigated 119 psychiatric consultations for cancer patients in a one year period. The assessment covered demographics and cancer diagnosis, psychiatric diagnosis and proceedings. RESULTS: One third of all patients were treated for hematological cancer, followed by lung cancer. Depression was the most common psychiatric disorder. One third of all patients with hematological cancer were diagnosed with depression, followed by delirium. Inpatient psychiatric treatment and psychotherapy were most commonly recommended by the consultant psychiatrist. Furthermore, 80.2% of all patients received recommendations for medication with antidepressants. CONCLUSION: Our data showed that the CLP provides an important service of detecting and initiating early and appropriate treatment for cancer patients with comorbid psychiatric disorders by directing patients to the relevant treatment procedure or facility.

["Lithium in the treatment of old age depression. What are the pros and cons?"] / "Lithium in der Behandlung der Altersdepression. Was spricht dafür, was dagegen?".

OBJECTIVE: Augmentation with lithium is one of the treatment options in therapy-resistant depression. This review presents the current data concerning the use of lithium in elderly patients with unipolar depression. METHOD: Through a selective literature search in the database PubMed, 15 relevant articles were identified and included. RESULTS: Both the clinical trials and reviews report in favor of lithium augmentation in elderly patients. Remission rates and response rates are high. Kidney damage, a feared side effect, is rarely seen. Even over longer periods of use, lithium is effective; however, close monitoring under laboratory tests must be carried out. CONCLUSION: Lithium represents an effective drug in the treatment of unipolar old age depression. Its use in daily clinical practice is therefore highly recommended.

Comparing consultation-liaison psychiatrist's and neurologist's approaches to delirium - A retrospective analysis.

OBJECTIVE: To compare the diagnostic, management, and treatment recommendations made by consultation-liaison psychiatrists (CLP) and neurologists (CLN) for suspected delirium and to investigate factors that may have influenced the choice for a particular consultation service. METHOD: In this retrospective case analysis, we screened the files of 1882 (CLP: 1112, CLN: 770) inpatients seen by CLP and CLN at the Charité - University Medicine, Berlin, Germany, in 2013. This revealed a total of 148 (CLP: 99, CLN: 49) delirium patients. Information found on the consultation form and in the patients' files was used for data collection and subsequently analyzed. RESULTS: Intensive care and surgical units preferably called CLP, while internists consulted more CLN and patients suffering from neurological or psychiatric preconditions were more often seen by the respective specialist. Despite no significant difference between psychomotor activity levels among the groups, CLP recommended significantly more pharmacological interventions (p = 0.000) and CLN ordered significantly more diagnostic procedures (p = 0.000). CONCLUSION: Our results show considerable differences between CLP and CLN treatment recommendations, which may indicate a conflicting approach to delirium work-up, not accountable to unequal patient characteristics. These preliminary results are not conclusive and should be followed up by high evidence level research.

Psychiatric liaison consultations of patients without psychiatric illness in a general hospital in Germany: a retrospective analysis.

The aim of the study was to explore the utilization of consultation-liaison psychiatric (CLP) service among nonpsychiatric patients in a general hospital. A retrospective analysis was conducted on all patients seen by the CLP in 2013. In 66 (5.9 %) of these 1112 consultations, no psychiatric diagnosis could be identified. These cases were analyzed by department of referral, assumed psychiatric symptoms, consensus with the symptoms found by the CLP, and recommended procedures. Assumed depressive symptoms, suicidal ideations and "difficult" behavior were the predominant reasons for CLP referrals. As the results suggest, CLP service was mostly "overprovided" because of uncertainty about the working areas of psychiatrists or overestimation of the severity of symptoms. These findings emphasize the importance to develop more precise guidelines for CLP services and that it could be worth striving for a more profound psychiatric training for nonpsychiatric physicians to achieve an optimal treatment for patients.

Psychiatric consultations and therapy recommendations following a suicide attempt in a general hospital and their associations with selected parameters in a 1-year period.

OBJECTIVE: Our study aims to determine the frequency and distribution of suicide attempts according to the patients' characteristics and type of suicide attempt as well as the method of treatment proposed by the consultation-liaison service in a general hospital. METHODS: This retrospective naturalistic study covers a 1-year period (2012), during which 51 suicide attempters were hospitalised in the Charité Berlin, Campus Benjamin Franklin, Germany. The following data were analysed: method of suicide, account of prior psychiatric history and medication, as well as the acute psychiatric diagnosis and treatment - including pharmacotherapy. RESULTS: Most of the patients were diagnosed with a psychiatric illness. Major depressive disorder was the most frequent diagnosis in consultation. Treatment recommendations more often entailed further psychiatric treatment than medication. In the cases where medication was indeed given, benzodiazepines were the most frequently prescribed. CONCLUSIONS: Most of the suicide attempters needed further therapy in psychiatric hospitals. A specialised pharmacotherapy (antidepressants, mood stabilisers) was rarely recommended by the psychiatric consultation service. The psychiatric consultation and therapy recommendations are important in guiding future acute treatment procedures.

Adjunctive lithium treatment in the prevention of suicidal behavior in patients with depression and comorbid personality disorders.

OBJECTIVE: Patients with both major depression and personality disorders have a high risk of suicidal behavior. Lithium is meant to have anti-suicidal properties in patients with affective disorders. The anti-suicidal effect of lithium in patients with affective disorders and comorbid personality disorders has not been investigated yet. METHODS: A post-hoc analysis of a subsample of patients with depression and comorbid personality disorder (PD) and a recent suicide attempt (n = 19) from the prospective, placebo-controlled lithium intervention study (N = 167), was conducted. RESULTS: Three patients in the lithium group (n = 8) and two patients in the placebo group (n = 11) presented a suicide attempt throughout the course of the study. No differences related to suicidal behavior could be detected between the placebo group and the group with lithium intervention. CONCLUSIONS: On the basis of the small sample size, among patients with comorbid PD, lithium does not seem to have an effect on suicidal behavior in contrast to patients with affective disorders without comorbid PD.

Comparative efficacy and acceptability of existing pharmacotherapies for delusional disorder: a retrospective case series and review of the literature.

UNLABELLED: Delusional disorder is an uncommon, yet not rare, psychotic disorder. Because of the distinct lack of high-evidence-level research conducted in this area, no definitive clinical guidelines are available on its treatment. The aim of this article was to summarize the current literature on the pharmacological treatment of delusional disorder in the form of a review, as well as to analyze a series of 6 cases treated at the Department of Psychiatry at "Charité-University Medicine Berlin, Campus Benjamin Franklin" between 2005 and 2011; in each case paying special attention to the relative efficacy and acceptability of the antipsychotics used. REVIEW: A MEDLINE search was conducted to capture all articles on the treatment of delusional disorder published since 2004. After viewing titles and abstracts, these articles were then assessed for relevance. CASE SERIES: The files of 6 cases of delusional disorder treated at the previously mentioned clinic were analyzed and information regarding the type of medication, dose, and duration of treatment as well as adverse effects was extracted and summarized. In line with previous studies, it was found that delusional disorder has a moderate prognosis when adequately treated and that noncompliance is often the reason for poor treatment results. Various novel antipsychotics as well as a combination of medication treatment and psychotherapy produced positive results. Generally, adverse effects were easily managed by a reduction in dose or a switch to another antipsychotic, and it was often necessary to try out a number of antipsychotics before arriving at a satisfactory solution.

Childhood maltreatment and adult proinflammatory status in patients with major depression.

BACKGROUND: An increasing body of research considers the immunological effects of major depression. It remains an open question, whether depression itself acts in an immunomodulatory fashion or whether other factors related to depression result in these immunological effects. Regardless, major depression is often the result of early life stress, the implications of which are not satisfactorily understood. SUBJECTS AND METHODS: Early life stress was retrospectively evaluated in 25 depressed inpatients via the CTQ (Childhood Trauma Questionnaire). Its impact on immunological biomarkers (fibrinogen, SAA, CRP, adiponectin, TNF-α, resistin, and sE-selectin) in adulthood was assessed via multiple regression analyses. Parental bonding was assessed via the PBI (Parental bonding questionnaire), severity of depression with the HDRS-17 (Hamilton-Depression-Rating Scale). RESULTS: Nearly all patients had experienced a parental style of affectionless control. Physical neglect significantly predicted fibrinogen levels (R(2)=0.42, adjusted R(2)=0.27, ß=0.56, p=0.04). Severity of depression was not associated with immune markers. CONCLUSION: Childhood maltreatment was linked to fibrinogen levels in our sample. Thus, inflammation may be an important mechanism mediating the adverse effects of early life stress on adult health in patients with major depression.

Quetiapine as combination treatment with citalopram in unipolar depression with prominent somatic symptoms: a randomised, double-blind, placebo-controlled pilot study.

BACKGROUND: Patients with major depressive disorder (MDD) accompanied by physical symptoms may be less responsive to antidepressant treatment. Quetiapine has been evaluated in the treatment of bipolar depression and has been recently approved as an add-on therapy for unipolar depression. Less is known about the efficacy of combination therapies in patients suffering from MDD with somatic symptoms. The aim of the present study was to evaluate the efficacy of quetiapine as adjunctive therapy to the SSRI citalopram in patients with MDD and somatic complaints. SUBJECTS AND METHODS: 41 inpatients with nonpsychotic DSM-IV MDD experiencing significant symptoms of somatic distress as defined by a baseline score on the SCL-90-R somatization subscale greater one standard deviation above adult nonpatient norms were randomly assigned to receive either citalopram 40 mg/day plus placebo (n=20) or citalopram 40 mg/day plus quetiapine, 300 to 600 mg/day (n=21) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. RESULTS: Mean changes in HDRS scores from baseline to week 6 using last-observation-carried-forward methods were -12.3±6.2 and -10.7±5.1 in the citalopram-quetiapine and citalopram-placebo group, respectively. Remission rates were significant higher in the citalopram-quetiapine-group (41.1%) than in the citalopram-placebo-group (26.3%), respectively. CONCLUSIONS: Although quetiapine as add-on to citalopram did not separate statistically from placebo on the HDRS score in improving depressive symptoms and somatic symptoms in patients with MDD and prominent somatic complaints, higher remission rates and other second outcome parameters showed advantages for quetiapine. Larger, double-blind, placebo-controlled trials of quetiapine as augmentation therapy in MDD with somatic symptoms are warranted.

Therapy Strategies for Late-life Depression: A Review.

BACKGROUND: Depression in the elderly requires different treatment options because therapies that are commonly used for depression in younger patients show different effects later in life. Treatment options for late-life depression (LLD) are summarized in this article. METHODS: A literature search in Medline/PubMed performed in June 2020 identified 83 relevant studies. RESULTS: Pharmacotherapy with selective serotonin reuptake inhibitors can be an effective first-line treatment in LLD, but >50% of elderly patients do not adequately respond. Switching to other selective serotonin reuptake inhibitors or augmenting with mood stabilizers or antipsychotics is often effective in achieving a therapeutic benefit. Severely depressed patients with a high risk of suicidal behavior can be treated with electroconvulsive therapy. Psychotherapy provides a measurable benefit alone and when combined with medication. LIMITATIONS: LLD remains an underrepresented domain in research. Paucity of data concerning the effect of specific therapies for LLD, heterogeneity in the quality of study designs, overinterpretation of results from meta-analyses, and discrepancies between study results and guideline recommendations were often noted. CONCLUSIONS: Treating LLD is complex, but there are several treatment options with good efficacy and tolerability. Some novel pharmaceuticals also show promise as potential antidepressants, but evidence for their efficacy and safety is still limited and based on only a few trials conducted to date.

Pathways linking early life stress, metabolic syndrome, and the inflammatory marker fibrinogen in depressed inpatients.

BACKGROUND: Previous research has shown that metabolic syndrome as well as early life stress can account for immunoactivation (e.g. in the form of altered fibrinogen levels) in patients with major depression. This study aims at assessing the relationship between components of metabolic syndrome, early life stress and fibrinogen levels, taking the severity of depression into consideration. SUBJECTS AND METHODS: Measures of early life stress and signs of metabolic syndrome were collected in 58 adult inpatients diagnosed with depression. The relationships between the factors were assessed by means of path analyses. Two main models were tested: the first model with metabolic syndrome mediating between early life stress and fibrinogen levels and the second model without the mediating effect of metabolic syndrome. RESULTS: The first model was not supported by our data (χ²=7.02, df=1, p=0.008, CFI=0.00, NNFI=-9.44, RMSEA=0.50). The second model however provided an excellent fit for the data (χ²=0.02, df=1, p=0.90, CFI=1.00, NNFI=2.71, RMSEA=0.00). Extending the models by introducing severity of depression into them did not yield good indices of fit. CONCLUSIONS: The developmental trajectory between early life stress and inflammation appears not to be mediated by metabolic syndrome associated factors in our sample. Possible reasons including severity and type of early life stress, as well as potential epigenetic influences are discussed.

Stimulus pulse-frequency-dependent efficacy and cognitive adverse effects of ultrabrief-pulse electroconvulsive therapy in patients with major depression.

BACKGROUND: : Electroconvulsive therapy (ECT) is a highly effective treatment for major depression. New ECT devices with shorter pulse widths seem to induce seizures more effectively at a lower seizure threshold and with fewer cognitive adverse effects. Suprathreshold right unilateral (RUL) ultrabrief-pulse ECT with pulse widths between 0.25 and 0.30 millisecond seem to be especially effective with regard to efficacy and cognitive adverse effects. A lower pulse frequency (50 pulses per second) in RUL ECT was found to be more efficient than a higher pulse frequency (200 pulses per second) in inducing seizures. However, effective stimulus dose can often be achieved only with high stimulus frequency, whereas the impact of increased stimulus frequency on antidepressant efficacy and cognitive adverse effects is not known. METHODS: : Forty patients with major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomly assigned to 2 groups of 20 patients each and stimulated with either 40 or 100 Hz with equal initial stimulus doses in 9 sessions of suprathreshold RUL ultrabrief-pulse ECT. Depressive symptoms and measures of verbal and working memory were assessed for both groups. RESULTS: : Patients in the 40-Hz condition showed significantly more improvement in Hamilton Rating Scale for Depression scores compared with patients in the 100-Hz condition after 9 ECT sessions. Frequency group had no significant impact on measures of verbal and working memory. CONCLUSIONS: : Within the discussed limitations, our preliminary data suggest an advantage for administering stimulus dose in suprathreshold RUL ultrabrief-pulse ECT with a lower stimulus frequency (40 Hz) as compared with a higher frequency (100 Hz). Further studies are needed to assess whether increasing pulse widths or frequency is the better option for augmenting stimulus dose once other stimulus parameters are at a maximum.

Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study.

OBJECTIVE: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks. RESULTS: After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS. CONCLUSIONS: Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram.