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.

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.

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.

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.

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.

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.

[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.

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.

Antimicroglia antibodies in sera of Alzheimer's disease patients.

BACKGROUND: Immune mechanisms seem to contribute to the degenerative process in Alzheimer's disease. Antibodies directed against animal brain tissue were found in sera of Alzheimer's patients. METHODS: Antibodies were measured in sera of 25 Alzheimer's patients and a comparison group of 25 age- and sex-matched controls. Sera were tested for their immunological response to various brain structures of postmortem human brain tissue. RESULTS: In 8 patients with Alzheimer's disease perinuclear antibodies directed against microglia were found in amygdala and frontal cortex. In the control group 1 subject showed antibody binding to microglia. CONCLUSIONS: Perinuclear antibodies to microglia may play a role in tissue destruction of Alzheimer's disease. These data add to the evidence that immune mechanisms play a role in the pathophysiology of Alzheimer's disease.

Effect of carbamazepine on agitation in Alzheimer's inpatients refractory to neuroleptics.

BACKGROUND: Agitation in Alzheimer's disease remains a principal problem in the clinical management of elderly patients. Neuroleptic medication appears to have modest efficacy in controlling behavioral symptoms in dementia patients. Carbamazepine has been reported to decrease agitation associated with various psychiatric disorders and to reduce neuroleptic side effects. METHOD: In an open prospective study, the effects of carbamazepine on agitation, hostility, and uncooperativeness were investigated in 15 severely demented Alzheimer's inpatients who had failed to respond to prior treatment with neuroleptics. Depending on clinical efficacy and tolerability of carbamazepine treatment, concomitant medication with haloperidol was initiated. Severity of psychopathologic symptoms was assessed by the Brief Psychiatric Rating Scale during the study period of 4 weeks. RESULTS: In 2 subjects, carbamazepine treatment was discontinued because of leukopenia and allergic reactions. A significant improvement in factor scores activation and hostility was observed after 4 weeks. Ten patients received concomitant medication with haloperidol. CONCLUSION: Carbamazepine may be effective in treating agitation in severely demented Alzheimer's inpatients refractory to neuroleptic medication alone. The combination of carbamazepine and haloperidol seems to be promising in clinical management of elderly Alzheimer's patients.

Motor activity and perception of sleep in depressed patients.

Subjectively experienced sleep patterns often differ from observed sleeping behavior in insomniacs. Sleep patterns have been evaluated by measurements of motor activity in healthy subjects and insomniacs, but results may depend on the insomnia subtype. Sleep disturbances are frequent complaints in depression, but the influence of psychopathology on activity measurements remains elusive. Therefore, the relationship between reported sleep complaints and motor activity was studied in patients with major depression. Severity of depression was documented in depressed inpatients by observer-(HAMD) and self-rated scales (DACL, SHAPS-D). Self-reports of sleep were obtained by Pittsburgh Sleep Quality Index (PSQI) and daily sleep logs (DSL). Motor activity was continuously recorded over 72 h by actigraphy. 'Good' sleepers showed less motor activity during the night compared to 'poor' sleepers (p<0.01). Patients with high HAMD scores (> or = 18) showed greater nocturnal motor activity and less sleep quality compared to patients with low HAMD scores (p<0.01). When controlling for age and severity of depression, partial correlation was found to be significant between perceived daily sleep quality and nocturnal motor activity (r = -0.63, p<0.01). There was a significant effect of nocturnal motor activity as a covariate on disturbances of subjective sleep quality and severity of depression as the main effect (p<0.01). In depressed patients, nocturnal motor activity seems to be an indicator of experienced sleep disturbances. The results warrant further controlled studies to evaluate the role of psychological factors for objective measurements and subjective perception of sleep patterns.

Spatiotemporal gait patterns during over ground locomotion in major depression compared with healthy controls.

Alterations of locomotion are frequent, observable features of patients suffering from depression and have been investigated in these patients by actigraphy, cinematography and ground reaction forces. However, spatiotemporal parameters and neurophysiological mechanisms of gait have not yet been studied in depth in depression. The relationship between spatial and temporal parameters may yield insight into the pathophysiology of altered movements in depression. Therefore, gait patterns were quantitatively assessed and analysed in depressed subjects (n=16) and compared to matched healthy controls. Spatiotemporal gait parameters were measured during over ground walking at self-selected walking speed on a walkway previously validated in healthy subjects and used for orthopaedic and neurological patients. Compared to controls, depressed patients showed significantly lower gait velocity (p<0.001), reduced stride length (p<0.005), double limb support (p<0.005) and cycle duration (p<0.005). There was a significant correlation between cadence and gait velocity in depressed patients (r=0.51, p<0.05), but not in healthy controls (r=0.11, p>0.05). In patients with major depression, reduced gait velocity was associated with stride hypometria and increased cycle duration. Velocity was associated with cadence in depressed patients but not in healthy controls. The results may indicate possible deficiencies in the motor control system in depression. These first results about alterations of spatiotemporal gait patterns in depression warrant further longitudinal and experimental studies.

Timing of movements in depressed patients and healthy controls.

BACKGROUND: Psychomotor disturbances are fundamental psychopathological features of major depression and observable components of behaviour. Human behaviour is segmented into action units with duration of a few seconds due to central nervous motor processing. Timing may depend on cognitive and emotional functions which are affected in depression. Therefore, time structure of action units in depressed patients was compared to healthy controls. METHODS: Included were patients with major depression and melancholic features. Upper limb movements (total n = 566) of depressed patients and matched controls were evaluated using videotaped interviews and frame-by-frame analysis with a temporal resolution of 40 ms. RESULTS: Behaviour of depressed patients in interview sessions was organised in action units with a narrow time span of only a few seconds. Single, non-repetitive action units were significantly shorter (median = 1.20 s) and repetitive units longer (median = 4.92 s) in patients compared to controls (median = 2.08 and 2.96, respectively). LIMITATIONS: Behaviour in interview sessions might differ from activities of daily living. DISCUSSION: Altered temporal segmentation of movements appears to be an observable, measurable sign of melancholic depression and may allow further insights in pathophysiological dysfunctions of the disease. Clinical implications of these motor changes for differential diagnosis, course and treatment of depression are discussed and need further evaluation.

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.

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.

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.

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.