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Biomedical subjects

I Schweitzer

Publications and source records attributed to I Schweitzer.

At least 37 records · Page 2Linked to original sources

Risk of adverse events with the use of augmentation therapy for the treatment of resistant depression.

Augmentation therapy is used for those situations where a patient's depression is either treatment-resistant, or partially and/or insufficiently responsive to treatment. It also may be used to attempt to induce a more rapid treatment response. Using drugs together may increase the risk of adverse effects, through potentiation of existing adverse effects or alterations in plasma concentrations of the drug. It is important that clinicians are aware of potential risks of augmentation therapy. Lithium augmentation of a tricyclic antidepressant is relatively well tolerated and the dangers are no greater than using these medications on their own. There are also no reports of serious adverse events when lithium is added to a monoamine oxidase inhibitor. With lithium augmentation of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) therapy there have been case reports of the development of a central serotonin syndrome, and thus caution must exercised. A serious concern when using a tricyclic antidepressant to augment an SSRI is the effect of the SSRI on the cytochrome P450 system and the resulting significant increase in tricyclic antidepressant blood concentrations. Augmentation with thyroid hormones appears to be well tolerated and effective. Case reports and open studies indicate that augmentation with buspirone and the psychostimulants, carbamazepine and valproic acid (valproate sodium) is effective and results in minimal adverse effects. However, there is no empirical evidence supporting these results. Recent work supports the tolerability and efficacy of pindolol augmentation. Considerable caution should be exercised when combining psychotropic drugs. The practitioner should only do so with a full knowledge of the compounds involved and their pharmacological properties.

Antidepressive Agents↗

Correlates of aggressive behaviour in schizophrenia: an overview.

OBJECTIVE: This review aims to critically evaluate the reported biological, psychological and social correlates of aggression in schizophrenia and to delineate those correlates which could be of use clinically and those which require further research. METHOD: The literature from 1974-1996 was searched using Psychlit and supplemented by suggestions from senior members of the authors' Department. RESULTS: Past history of aggression, psychopathology, extrapyramidal side effects of neuroleptic medications, substance abuse, reduced serotonin function, antisocial and impulsive personality traits, neurological/neuropsychological deficits, electroencephalography, neuroimaging abnormalities and environmental factors were all found to be correlated with aggressive behaviour in schizophrenia. However, there are many methodological limitations of previous studies in this field, often leading to inconsistent and inconclusive findings. CONCLUSIONS: Some tentative conclusions regarding clinically useful predictors of aggression in schizophrenia can be drawn at this stage. There is a need for methodological limitations of previous studies to be overcome before more firm conclusions can be reached.

Aggression↗

Aggressive behaviour in schizophrenia: role of state versus trait factors.

The objective of this article was to elucidate the relative importance of state vs. trait factors in determining aggressive behaviour in schizophrenia. Thirty-one aggressive schizophrenia patients in rehabilitation wards were compared with 31 matched non-aggressive patients with respect to their psychopathology, phenomenologies of hallucinations and delusions, neuroleptic motor side effects, history of aggression and personality traits. Significant differences between the two groups were found in relation to psychopathology, affective responses to hallucinations/delusions, history of aggression and personality traits, but there were no significant differences regarding neuroleptic motor side effects. The effects of history of aggression as well as personality traits were independent of and similar to the total level of psychopathology, but were much smaller when compared to those of negative affective responses to hallucinations/delusions.

Adult↗

Violence in schizophrenia: role of hallucinations and delusions.

The study examines the relationship between hallucinations/delusions and violent behaviour in a sample of long-stay inpatients with chronic schizophrenia. Thirty-one subjects defined as violent and meeting DSM-111-R criteria for schizophrenia were compared with 31 matched non-violent schizophrenia patients with respect to detailed phenomenologies of auditory hallucinations using the Mental Health Research Institute Unusual Perceptions Schedule (Carter and Copolov, 1993; Carter et al., 1995) and delusions using the Maudsley Assessment of Delusions Schedule (Taylor et al., 1994). Patients in the violent groups were significantly more likely to experience negative emotions, tone and content related to their voices than those in the non-violent group, whilst patients in the non-violent group were more likely to experience positive emotions, tone and content related to their voices. Patients in the non-violent group were significantly more likely to report success in coping with their voices. There was no association between command hallucinations and violent behaviour. Patients in the violent group were more likely to hold persecutory delusional beliefs than those in the non-violent group, while patients in the non-violent group were likely to hold grandiose delusions than those in the violent group. Patients in the violent group were also more likely to report that the delusion made them feel angry, while those in the non-violent group were more likely to report that the delusion made them feel elated. The results suggest specific aspects of the phenomenologies of hallucinations and delusions that should be clinically assessed to determine the likelihood of violence as a result of such psychotic symptoms.

Adult↗

Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia.

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.

Adult↗

Clinical, magnetic resonance imaging and endocrinological differences between delusional and non-delusional depression in the elderly.

OBJECTIVE: To investigate neuroradiological, endocrinological and clinical differences between delusional and non-delusional depression. DESIGN: A cross-sectional study of depressed subjects. SETTING: Melbourne, Australia. PARTICIPANTS: Sixty-one subjects (inpatients) over the age of 55 meeting DSM-III-R criteria for major depression of whom 22 had delusional subtype of depression. MEASURES: Clinical assessment, including documentation of vascular risk factors. Cognitive assessment by the Cambridge Cognitive Examination (CAMCOG). Magnetic resonance imaging (MRI) scans were performed on a 0.3 Tesla scanner with temporal lobe atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) rated visually on 4-point scales. A standard 1 mg dexamethasone suppression test (DST) was performed. RESULTS: Subjects with delusional depression had significantly more vascular risk factors than those without delusions. There were no differences in measures of temporal lobe atrophy, PVL, DST results or cognitive test scores, though there was a non-significant trend for DWML to be more prevalent in those with delusions. Delusional depression was associated with a shorter duration of history and more frequent treatment with ECT. CONCLUSIONS: The increase in vascular risk factors and trend towards greater DWML on MRI suggests an organic contribution to delusional depression in the elderly. In contrast to some previous reports, we found no differences in cortical MRI appearance or neuroendocrine measures between groups.

Aged↗

Temporal lobe magnetic resonance imaging can differentiate Alzheimer's disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment.

BACKGROUND: Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined. METHODS: We studied 222 subjects using T1 weighted MRI with 5.1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N = 40); DSM-III-R major depression (N = 61); NINCDS/ADRDA DAT (N = 77) and OTHER (N = 44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of 'memory complainers'). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0-3 scale by two experienced neuroradiologists blind to clinical diagnosis. RESULTS: Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history. CONCLUSIONS: Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

Age Factors↗

Does transfusion practice affect mortality in critically ill patients? Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian Critical Care Trials Group.

In 4,470 critically ill patients, we examined the impact of transfusion practice on mortality rates. As compared with survivors, patients who died in intensive care units (ICU) had lower hemoglobin values (95 +/- 26 versus 104 +/- 23 g/L, p < 0.0001) and were transfused red cells more frequently (42.6% versus 28.0%, p < 0.0001). In patients with cardiac disease, there was a trend toward an increased mortality when hemoglobin values were < 95 g/L (55% versus 42%, p = 0.09) as compared with anemic patients with other diagnoses. Patients with anemia, a high APACHE II score (> 20), and a cardiac diagnosis had a significantly lower mortality rate when given 1 to 3 or 4 to 6 units of allogeneic red cells (55% [no transfusions] versus 35% [1 to 3 units] or 32% [4 to 6 units], respectively, p = 0.01). Adjusted odds ratio (OR) predicting survival were 0.61 (95% CI; 0.37 to 1.00, p = 0.026) after 1 to 3 units and 0.49 (95% CI; 0.23 to 1.03, p = 0.03) after 4 to 6 units compared with nontransfused anemic patients. In the subgroup with cardiac disease, increasing hemoglobin values in anemic patients was associated with improved survival (OR = 0.80 for each 10 g/L increase, p = 0.012). We conclude that anemia increases the risk of death in critically ill patients with cardiac disease. Blood transfusions appear to decrease this risk.

APACHE↗

A prospective study of assaults on staff by psychiatric in-patients.

This study determined the prevalence and features of assaults on staff, compared them with other aggressive incidents by psychiatric in-patients, and studied their relationship with the ward atmosphere. There were 181 physical assaults among 279 staff in two months, i.e. 389 assaults per 100 staff per year. A few patients were responsible for the majority of the assaults. Most assaults were triggered off by staff-patient interaction. About one-third of the staff were significantly psychologically shaken by the incidents. Patients were more likely to be provoked and used more severe means of aggression against staff than against other targets of aggression. There were no significant differences between the characteristics of patients who assaulted staff and those who had other targets of aggression.

Adolescent↗

Studies of aggressive behaviour in schizophrenia: is there a response bias?

Of 73 patients who met selection criteria to enter into a study on aggressive behaviour in schizophrenia, 11 patients (15.1%) did not participate. The participants and non-participants were similar in age, gender ratio and proportion who had aggressive behaviour. The participants, however, had a longer duration of illness, a longer duration of current admission, were more likely to suffer from residual schizophrenia, but less likely to suffer from disorganized schizophrenia and were less severely ill than the non-participants. These results indicate the need, in studies of aggressive behaviour in schizophrenia, to consider non-response bias as a confounding variable.

Adult↗

Aggressive behaviour in schizophrenia: the role of psychopathology.

OBJECTIVE: The aim of this study was to determine the psychopathological correlates of aggressive behaviour in schizophrenia. METHOD: Thirty-one aggressive patients in rehabilitation wards meeting DSM-III-R criteria for schizophrenia were compared with 31 matched non-aggressive patients in relation to their psychopathology using the Clinical Global Index (CGI), Positive and Negative Symptoms scale (PANSS) and the Montgomery-Asberg Depression Rating Scale. RESULTS: The aggressive group had significantly higher CGI, positive symptom, negative symptom, general psychopathology and total PANSS scores than the non-aggressive group. The two groups could be distinguished by three sets of symptoms: symptoms with verbal or/and physical aggression as part of their definition; symptoms suggesting frontal lobe impairment; and excitement. The two groups did not differ in their level of depressive symptomatology. CONCLUSIONS: The aggressive group were overall more ill than the non-aggressive group, and the former could be distinguished from the latter by certain aspects of their psychopathology.

Adult↗

A review of the use of augmentation therapy for the treatment of resistant depression: implications for the clinician.

OBJECTIVE: To critically review the literature on augmentation therapy in resistant depression in order to assist the clinician to make a reasoned choice. Augmentation therapy is defined as the addition of a second agent to an existing antidepressant regimen with the aim of achieving improved clinical response. METHOD: The available literature which related specifically to currently popular augmentation strategies in treatment resistant depression for the past 20 years was examined. The scientific evidence supporting the efficacy of these regimens and their safety was reviewed. RESULTS: Considerable research on lithium augmentation has been undertaken, and on triiodothyronine augmentation to a lesser degree. A number of other drugs have been trialed as augmentation agents with claims of success; however, most of the evidence supporting these agents is anecdotal and in the form of case reports. There are very few well-performed double-blind placebo-controlled studies of augmentation therapy. CONCLUSIONS: Because of possible complex pharmacodynamic and pharmacokinetic interactions, augmentation therapy is not without its potential complications. Lithium augmentation of tricyclic antidepressants can be recommended as a safe and effective strategy and there is a body of scientific evidence supporting the addition of T3 as an effective augmentation agent. Recent research with pindolol augmentation of selective serotonin re-uptake inhibitors (SSRIs) is encouraging, but these findings require replication. There is no empirical evidence supporting buspirone, carbamazepine, sodium valproate, methylphenidate or amphetamine as effective augmentation agents, or that adding a tricyclic to a SSRI has usefulness in relieving depressive symptoms. There is a need for considerable research in this area, with more prospective well-controlled placebo studies.

Antidepressive Agents↗

Magnetic resonance imaging correlates of memory impairment in the healthy elderly: association with medial temporal lobe atrophy but not white matter lesions.

OBJECTIVE: To investigate the neuroradiological correlates of age-related cognitive decline in the elderly. DESIGN: A sample of healthy control subjects underwent magnetic resonance imaging (MRI) scanning and cognitive testing. SETTING: Melbourne, Australia. PARTICIPANTS: 40 volunteers over the age of 55 who were spouses of subjects seen in a hospital memory clinic, subjects from a register of normal volunteer subjects (not staff) kept for research purposes or residents of a retirement hostel. MEASURES: Hippocampal and amygdala (HA) atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: After controlling for age and education, lower scores on the memory subscale of the CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL. CONCLUSIONS: HA atrophy on MRI is associated with impaired memory performance in the healthy elderly, while PVL and DWML are not. Further study should determine whether HA atrophy is a risk factor for developing dementia.

Aged↗

Does hippocampal atrophy on MRI predict cognitive decline? A prospective follow-up study.

OBJECTIVES: To investigate whether the presence of hippocampal atrophy (HCA) on MRI in Alzheimer's disease (AD) leads to a more rapid decline in cognitive function. To investigate whether cognitively unimpaired controls and depressed subjects with HCA are at higher risk than those without HCA of developing dementia. DESIGN: A prospective follow-up of subjects from a previously reported MRI study. SETTING: Melbourne, Australia. PARTICIPANTS: Five controls with HCA and five age-matched controls without HCA, seven depressed subjects with HCA and seven without HCA, and 12 subjects with clinically diagnosed probable AD with HCA and 12 without HCA were studied. They were followed up at approximately 2 years with repeat cognitive testing, blind to initial diagnosis and MRI result. MEASURES: HCA was rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: No significant differences in rate of cognitive decline, mortality or progression to dementia were found between subjects with or without HCA. CONCLUSIONS: HCA was not found to be a predictor of subsequent cognitive decline in this series.

Aged↗

Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease.

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0.05 microgram/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0.044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

Adrenocorticotropic Hormone↗

Aggressive behaviour and extrapyramidal side effects of neuroleptics in schizophrenia.

The objective of this study was to determine whether extrapyramidal side effects of neuroleptics are associated with aggressive behaviour in schizophrenia. Thirty-one physically aggressive patients meeting DSM-III-R criteria for schizophrenia were compared with 31 matched non-aggressive patients in relation to their extrapyramidal side effects, including drug-induced parkinsonian (DIP) symptoms, akathisia and tardive dyskinesia. The aggressive group had significantly more severe DIP side effects than the non-aggressive group, but the association disappeared when level of psychopathology was controlled for. The aggressive group had more severe akathisia than the non-aggressive group, but the difference was not statistically significant. The two groups did not suffer in the severity of tardive dyskinesia. There was no significant, independent effect of extrapyramidal symptoms on aggressive behaviour in our sample of schizophrenic patients.

Adolescent↗

Respiratory infections and the autumn increase in asthma morbidity.

Unexplained autumn increases in hospital admissions for asthma have been reported in many countries, including the United States, Canada, England and Wales. To investigate the role of infection, the association was tested between hospital admissions for asthma and respiratory infections among preschool children in Metropolitan Toronto, Canada during the period 1981 to 1989. The seasonal pattern in overall hospital utilization was assessed by admissions for nonrespiratory diseases. Time series analysis was used to remove potentially confounding temporal trends and the influence of correlated errors. A fourfold increase in asthma admissions occurred between July and October unaccompanied by similar increases in nonrespiratory admissions. Admissions began increasing during the third week of August, peaked during the third week in September, and slowly decreased during November and December. After adjusting for serial correlation, trends, climate, ambient air pollution and aeroallergens, the seasonal pattern of respiratory infection explained 14% of the variance in asthma admissions. Based on seasonal patterns, respiratory infection is the major identifiable risk factor for the large autumnal increase in asthma admissions.

Air Pollutants↗

A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease.

BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.

Aged↗