What are depressive symptoms in acutely ill patients with schizophrenia spectrum disorder?

BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.

Insight in schizophrenia-course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder.

BACKGROUND: To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. METHODS: Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale ("lack of insight and judgement"). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. RESULTS: Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p=0.0004), less suicidality (p=0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p=0.0012) at admission were identified to be significant predictors of poor insight at discharge. CONCLUSION: The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

BACKGROUND: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being. METHOD: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome. RESULTS: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission. CONCLUSIONS: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

A critical analysis and discussion of the appropriateness of the schizophrenia consensus remission criteria in clinical pharmaceutical trials.

BACKGROUND: The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS: The Remission in Schizophrenia Working Group's consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS: 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION: The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.

Time course of antipsychotic treatment response in schizophrenia: results from a naturalistic study in 280 patients.

OBJECTIVE: To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. METHODS: Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. RESULTS: The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. CONCLUSION: Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

Perspectives on recent advances in the understanding and treatment of Parkinson's disease.

There have been numerous important recent advances in our understanding of the causes of Parkinson's disease (PD), the treatments available and how these are best applied for the long-term management of patients. Novel genes causing familial PD have been discovered and mechanisms leading to cell dysfunction and death identified. The PD prodrome is now a subject of great interest and clinical markers are being defined that may in future, together with biochemical markers, support an early, pre-motor diagnosis of PD. This will become important as new therapies are developed to modify disease progression. In the interim, the optimization of existing therapies remains an important priority. The value of existing and novel continuous drug delivery systems in PD is seen as providing simplified regimens, maintenance of motor control, reduction in motor complications and improved patient adherence to drug use.

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study.

OBJECTIVE: To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS: Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS: Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION: The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.

Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures.

INTRODUCTION: Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS: The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS: When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION: The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

Dopamine agonists in the treatment of non-motor symptoms of Parkinson's disease: depression.

BACKGROUND: Psychiatric symptoms such as depression are common non-motor comorbidities of Parkinson's disease (PD). Depressive symptoms in patients with PD are a major complication that impairs quality of life independent of motor symptoms. The relationship between PD and comorbid depression is not completely understood. METHODS AND RESULTS: Evidence suggests that both PD and depression may be mediated by degeneration of the dopaminergic system. Recent and ongoing research is exploring the potential role of dopamine agonists in the treatment of depressive symptoms in patients with PD. CONCLUSION: Experimental studies suggest a primary relationship and the importance of dopaminergic mechanisms in PD and depression. Patients with PD and depression might benefit from a global approach. Thus, treatment with dopamine agonists promises to reduce motor complications as well as depressive symptoms, avoiding multiple drug interactions as well as possible antidepressant medication side effects.

Depressive symptoms in Parkinson's disease.

Depression occurs in approximately 45% of all patients with Parkinson's disease (PD), does not correlate with the stage of motor deficits, reduces quality of life independently of motor symptoms and appears to be underrated and undertreated. Anxiety and depression are the risk factors for the development of PD and may be present many years before the appearance of motor symptoms. Studies using functional imaging techniques indicate a primary relationship between depression and PD. Because of overlapping clinical symptoms, the diagnosis is mainly based on subjectively experienced anhedonia and feelings of emptiness. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the aetiology of depression in PD. Tricyclic and newer selective antidepressants including serotonin and noradrenaline reuptake inhibitors appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to be better tolerated because of their favourable side-effect profile. Experimental and clinical investigations indicate antidepressive effects for pramipexole. Placebo-controlled studies showed antidepressant effects of pramipexole in patients with different forms of depression. Various studies show that pramipexole improves depression in addition to motor symptoms in patients with PD. Because of the data available as well as clinical reasoning, pramipexole may be used as a first-line treatment in patients with PD and depression.

[Antidepressant effects of dopamine agonists. Experimental and clinical findings]. / Dopaminagonisten als Antidepressiva. Experimentelle und klinische Befunde.

Results of preclinical and clinical studies implicate that, in addition to serotonin and norepinephrin, dopaminergic mechanisms play a role in the pathogenesis and treatment of depression. Newer antidepressants such as bupropion, sertraline, and venlafaxine act as partial inhibitors of presynaptic dopamine reuptake. Experimental studies show that dopaminergic effects contribute to the development of anxiety, depression, and anhedonia. These studies revealed, among the new nonergot dopamine agonists, anxiolytic properties for ropinirole and anxiolytic, antidepressive, and antianhedonic effects of pramipexole which seem to relate to its specific action on D(2) and D(3) receptors in the mesolimbic system and prefrontal cortex. In addition, affective disorders may be associated with impairments of neuronal plasticity, and pramipexole seems to exert neurotrophic properties. Controlled and open studies in depressed patients with Parkinson's disease show therapeutic effects of dopamine agonists on motor deficits, anhedonia, and depression. Various dopamine agonists have been tested in open studies in patients with depression and may add to the spectrum of treatment options in mood disorders. Recently published placebo-controlled trials in small patient groups implicate that pramipexole is effective as additional treatment to mood stabilizers in I and II bipolar depression.

Kinetic tremor in Parkinson's disease--an underrated symptom.

Since the first description of the disorder which we now call "Parkinson's Disease" (PD) much has changed not only because of new therapeutic possibilities. Initially only the rest tremor was described. Today it is generally accepted that PD can be accompanied by different forms of tremor. Nevertheless the kinetic tremor is hardly examined and no attention is paid to it in clinical rating scales although it can already be found in old published drawings of PD-patients. To date instrumented investigations do not capture the most common kinetic tremor of PD that seems to be frequent under everyday life conditions. In order to assess the significance of kinetic tremor in PD, tremor during a spiral drawing task was investigated in an open study involving 870 patients. The results indicate that a combination of rest, postural and kinetic tremors constitute the most frequent tremor constellation in PD.

[Long-term effects of traumatic experiences on somatic and psychic complaints of German World War Two refugees]. / Langfristige Auswirkungen traumatischer Ereignisse auf somatische und psychische Beschwerden. Am Beispiel von Vertriebenen nach dem 2. Weltkrieg.

The effects of expulsion from German territories following World War Two have not been studied systematically, and little is known about long-term effects of this potentially traumatic experience. Via mail, 600 refugees from former German territories due to World War Two were asked to complete questionnaires about biographic data, somatic and psychic health (SCL-90-R questionnaire), and specific aspects related to traumatic experiences (post-traumatic stress disorder questionnaire). Of those contacted, 25% participated in the investigation. Of them, 9.8% fulfilled diagnostic criteria of post-traumatic stress disorder according to DSM IV. Only 1.8% of an age-matched control group met these criteria. Analysis of the SCL-90-R questionnaire showed higher scores for former refugees in somatic and psychic complaints than the control group. We show that expulsion following war may lead to symptoms of post-traumatic stress disorder and somatic and psychic complaints after more than 50 years. Our investigation supports the necessity of adequate care for subjects expelled from their home countries and the psychologically traumatised.

[Pramipexole in Parkinson disease. Results of a treatment observation]. / Pramipexol bei der Parkinson-Krankheit. Ergebnisse einer Anwendungsbeobachtung.

Pramipexole is a novel, internationally available selective nonergot D2 dopamine agonist. The effectiveness, tolerability, and safety of pramipexole have been extensively proven in controlled trials in patients in the early and advanced stage of Parkinson's disease as monotherapy and in combination with L dopa. These trials indicated specific activity against tremor, anhedonia, and depression. Therefore, the present prospective, multicenter postmarketing surveillance study evaluated for the first time to what extent the results from the controlled pramipexole trials could be replicated under routine conditions in neurological practice and clinics. Modern scales were applied for the assessment of tremor and mood, i.e., the Short Parkinson's Evaluation Scale (SPES), the Tremor Impact Scale (TIS), and the German version of the Snaith-Hamilton Pleasure Scale (SHAPS-D). In 298 German Centers, 657 Parkinson's patients (365 men, 292 women) in advanced disease stages were treated with pramipexole in combination with levodopa. The average ages (+/- SD) were 67 (+/- 8.9) years for men and 69 (+/- 9.4) years for females. Motor functioning, especially tremor, motor complications, depression, and activities of daily living improved highly significantly (P < 0.0005), including self-rating by the patients. The dosage of levodopa could be reduced on average by 8% (P < 0.0001). This might contribute to a slowing of the disease progression in the long run. Dropouts due to side effects were observed only in 3.5% of the patients. Using new assessment scales suitable for routine application allowed confirmation of the results from controlled clinical trials with regard to tremor, anhedonia, and depression. The average daily dosage of pramipexole prescribed was 1.05 mg and thus was definitely lower than the average daily dosages of 2.35-2.66 mg used in controlled trials. This signifies that the option to adjust dosage according to effectiveness and tolerability under routine conditions yields a considerably lower incidence of adverse effects.

[Locomotion and depression. Clinical and physiological aspects of gait alterations in Parkinson's disease and major depression]. / Lokomotion und Depression - Klinik und Physiologie des Ganges bei Morbus Parkinson und affektiven Störungen -

BACKGROUND: Behavioral disturbances of patients with major depression manifest in various motor domains and are relevant for differential diagnosis, therapeutic interventions, as residual symptoms and possibly early manifestation of Parkinson's disease. Alterations of gait as the main component of locomotion are a clinically well-known motor phenomenon of depressed patients. Therefore, pathophysiology of gait disturbances, different methods to analyze gait and empirical findings in patients with major depression are summarized. METHODS: The current literature was examined including information of manufacturers, Medline, PubMed, PsychLIT and Excerpta Medica. Findings in healthy subjects, in Parkinson's disease, and in major depression are discussed in detail regarding specificity and clinical relevance. RESULTS: Kinematic analysis of gait regulation by videography, ultrasound, opto-electronic measures reveals information about disturbances in central nervous motor programming. Only few studies exist about quantitative data of gait alterations in patients with major depression. Results indicate disturbances in functions of the basal ganglia. CONCLUSIONS: Analysis of gait using modern technology yields information about cortical and subcortical dysfunctions. Empirical findings in major depression need further investigation regarding their relevance as residual symptoms, as response predictors, and as risk factors for manifestation of Parkinson's disease.

[Motor behavior in depression: applications and limitations of actigraphic analyses]. / Aktivität und Depression--Möglichkeiten und Grenzen aktigraphischer Verhaltensanalysen.

OBJECTIVE: Alterations of motor behavior in depression play a key role in psychosocial activities and interpersonal communication and are relevant for differential diagnosis and treatment. Functions and application of actigraphy and empirical findings in depression will be summarised and discussed. METHODS: The current knowledge retrieved from information of manufacturers, Medline, PsycLIT, and PSYNDEX regarding features of actigraphic equipment and clinical aspects of gross motor analysis in depression was examined. RESULTS: Actigraphy is a practical method to monitor and quantify gross motor activity, but setting variables including sensitivity or epoch length vary among commercially available instruments. Measures of motor activity in depressed patients are used for diagnosis, evaluation of sleep, and prediction of treatment response. CONCLUSIONS: Measurements of motor behavior by actigraphy can be used in depression for diagnostic procedures and treatment evaluation. The role of actigraphic setting variables needs further clarification. Actigraphy may be used for behavioral analysis including individual regulation of motor activity as an objective parameter for evaluation of depression and other psychiatric disorders.

[Disordered behavioral control in psychiatric illnesses. Neurophysiological aspects of impulsive behavior]. / Störung der Verhaltenskontrolle bei psychiatrischen Erkrankungen. Neurophysiologische Aspekte impulsiver Handlungen.

OBJECTIVE: Dysfunction of behavioral control represents a central component of many psychiatric disorders and may be connected with self-mutilating and antisocial behavior. However, only a few studies have investigated objective assessment and quantification of impulsive behavior, which is relevant for psychiatric practice and research. Because new techniques enable objective assessment of behavior generation and execution, the current knowledge about neurophysiological aspects of behavioral control is summarized. METHOD: The contemporary literature on neuronal mechanisms of initiation and execution of behavior and movements and new neurophysiological methods and findings are discussed in respect to their application in psychiatry. RESULTS: Behavior, defined as movements of a body in time and space, is the result of cortical and subcortical processes. These consist of two general components: (1) perception and selection of a stimulus and (2) execution of a movement, including decision and planning phases. Planning and execution, modulated by cognition and emotions, are dependent on the balance of inhibitory and excitatory aspects of behavior control. Combined detection of electrical brain activity and kinematic analysis of peripheral movements enables the analysis of control mechanisms. CONCLUSION: Impulsiveness and inhibition of behavior depend on neuronal control mechanisms which can be analyzed by neurophysiological methods. Objective assessment of impulsive behavior related to psychiatric disturbances including eating disorders, substance abuse, and personality disorders may clarify underlying neurobiological mechanisms and enable rational pharmaco- and psychotherapeutic interventions.

Comorbid anxiety and affective disorder in alcohol-dependent patients seeking treatment: the first Multicentre Study in Germany.

The goals of this study were to describe demographic variables, drinking history, and the 6-month prevalence of Axis I comorbidity among alcohol-dependent subjects in GERMANY: The variables: amount of alcohol consumption, age at onset of the first alcohol consumed, age at onset of daily alcohol consumption, age at onset of withdrawal symptoms and number of detoxifications were related to the different comorbid disorders and gender. In this study, 556 patients from 25 alcohol treatment centres were enrolled between 1 January 1999 and 30 April 1999. After a minimum of 10 days of sobriety patients who fulfilled ICD-10 and DSM-IV criteria of alcohol dependence were interviewed for data collection using the Mini-DIPS (German version of the Anxiety Disorders Interview Schedule) and a standardized psychosocial interview. The 6-month prevalence of comorbid Axis I disorders was 53.1%. Among the patients with comorbidity, affective and anxiety disorders were most frequent. Comorbid stress disorder was associated with an early start of drinking, an early beginning of withdrawal symptoms, highest number of detoxifications, and the highest amount of alcohol consumed. Female patients with anxiety disorder consumed more alcohol and started earlier than females without this comorbid disorder. The data do not answer the question of the pathogenesis of comorbid disorders and alcoholism, but indicate that stress disorders in alcoholic patients and anxiety disorders in female alcoholics influence the course and severity of alcoholism.