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Biomedical subjects

Isaac Schweitzer

Publications and source records attributed to Isaac Schweitzer.

17 recordsLinked to original sources

Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.

The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.

Adult↗

Recent advances in optimizing electroconvulsive therapy.

This review aims to summarize and critically evaluate the evidence for recent advances and alternative approaches in electroconvulsive therapy (ECT) technique. Novel developments in ECT research are also mentioned. An EMBASE literature search was undertaken of clinical trials, case reports and research updates on novel and alternative approaches in ECT practice and research, including alternative electrode placements, variations in stimulus configuration, and novel developments (magnetic seizure therapy, focal electrical stimulation). The evidence for these approaches is reviewed, and implications for the optimizing of ECT in clinical practice are discussed. Evidence from studies suggests that unilateral ECT be given at substantially suprathreshold doses (at least 6 times seizure threshold) for maximizing efficacy, while bilateral ECT is likely to be effective at doses of 1.5-2.5 times seizure threshold. There is some evidence to support the use of bifrontal ECT, although further research is required to establish its efficacy and side-effects relative to standard unilateral and bilateral electrode placements. Other alternative electrode placements have been minimally studied. More advantageous efficacy side-effect outcomes may be achieved by reducing the pulse width and/or frequency of the ECT stimulus. Lastly, novel developments using alternative means of seizure induction (magnetic fields, focal electrical stimulation) may hold promise for the future. Clinical practice should be guided by a careful appraisal of the available evidence for alternative approaches in ECT technique.

Electroconvulsive Therapy↗

A comparative study of sertraline dosages, plasma concentrations, efficacy and adverse reactions in Chinese versus Caucasian patients.

This prospective 6-week study examined the differences in dosage and steady state plasma concentrations of sertraline in Chinese versus Caucasian depressed patients. Two groups of Chinese patients from different geographical sites and a group of Caucasian patients were evaluated with clinical measures during an initial dose of 50 mg/day, with subsequent doses adjusted clinically. The results of 17 Australian Chinese (ACHI), 13 Malaysian Chinese (MCHI) and 15 Australian Caucasians (AC) were analysed. Despite controlling for weight, the AC subjects received a significantly higher dose than both the ACHI (P = 0.002) and the MCHI groups (P = 0.012). However, the mean sertraline concentration to dose ratios at weeks 1 and 6 were not significantly different between the three groups. Sertraline was effective and well tolerated in both ethnic groups with few adverse events. Although there was a lack of difference between groups in the pharmacokinetic results, Chinese depressed patients appeared to require lower dosages with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy. Further studies of the dosages, kinetics and adverse effects of selective serotonin reuptake inhibitors linked with genotyping are necessary.

Adult↗

An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels.

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.

Adult↗

A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients.

BACKGROUND: There is an increasing number of primary hyperparathyroidism (PHPT) patients with neuropsychological or psychiatric symptoms. Many of these patients do not have osseous or renal complications to satisfy the criteria for parathyroidectomy according to the NIH guidelines. OBJECTIVE: To assess whether there is any improvement in neuropsychological and mood symptoms following parathyroidectomy. PATIENTS AND DESIGN: Twenty PHPT patients undergoing parathyroidectomy and 20 orthopaedic controls matched for age, gender and estimated intelligence were subjects to pre and postoperative assessment of cognition and mood with a mean surgery-retest interval of 3 months. RESULTS: Using two tests of attentional flexibility [the Stroop test, the Digit symbol test of the Wechsler Adult Intelligence Scale-Revised (WAIS-R)], and two memory tests for prose and nonverbal material, no significant change was found between the groups when comparing scores before and after surgery. There was no improvement between pre and postoperative measures of verbal (dominant hemisphere) as opposed to visuo-spatial (nondominant hemisphere) function when compared to controls. There was no relationship between the reduction in serum calcium and the change in the neuropsychological measures postoperatively. CONCLUSION: This controlled, prospective study demonstrates no significant improvement in neuropsychological indices using objective, validated psychometric tools in an unselected cohort of PHPT patients. No relationship was found between serum calcium level and the degree of neuropsychological deficit. More studies are needed to assess whether the effect of parathyroidectomy is beneficial and sustainable in PHPT patients with neuropsychological symptoms alone.

Adult↗

Prolactin response to d-fenfluramine in combat-related post-traumatic stress disorder.

Central serotonergic function can be investigated by measuring the prolactin response to the serotonin releasing/uptake agent, d-fenfluramine. This study investigated the effect of diagnosis, depressive symptoms and history of alcohol or tobacco abuse or dependence on the d-fenfluramine test in combat-related post-traumatic stress disorder (PTSD). Male, non-hospitalized combat-exposed veterans diagnosed with PTSD (DSM-III-R) and a similarly aged combat-exposed control group were assessed for both PTSD and depressive symptoms and prolactin responses to a 30-mg d-fenfluramine challenge test. Ninety-five subjects were studied; 23 were controls, 46 subjects met the criteria for current PTSD and 26 for past PTSD. There were no significant differences between the three groups for baseline prolactin, peak prolactin, and time to reach peak, delta prolactin or area under the curve of the prolactin vs. time curve. Depressive symptoms and history of alcohol or tobacco abuse or dependence did not have a confounding effect on the prolactin responses to d-fenfluramine. This study suggests that a blunted prolactin response to d-fenfluramine may be a consequence of combat exposure rather than PTSD. To confirm this, further studies involving both healthy and combat-exposed control groups in addition to subjects with PTSD of similar ages are required.

Adult↗

Blunted growth hormone response to clonidine in post-traumatic stress disorder.

Hyperactivity of the sympathetic and noradrenergic systems is thought to be a feature of post-traumatic stress disorder (PTSD). Assessment of noradrenergic receptor function can be undertaken by measuring the growth hormone (GH) response to the alpha2-agonist clonidine. The aim of this study was to examine whether subjects with combat-related PTSD (with or without co-morbid depression) have a blunted growth hormone response to clonidine, compared to a combat-exposed control group. Twenty-three Vietnam veterans suffering from PTSD alone, 27 suffering from PTSD and co-morbid depression, and 32 veteran controls with no psychiatric illness were administered 1.5 microg/kg clonidine i.v. Plasma growth hormone was measured every 20 min for 120 min. The growth hormone response to clonidine was significantly blunted in the non-depressed PTSD group compared to both the depressed PTSD group and the control group as measured by peak growth hormone, delta growth hormone and AUC growth hormone. Subjects with PTSD and no co-morbid depressive illness show a blunted growth hormone response to clonidine. This suggests that post-synaptic alpha2-receptors are subsensitive. This finding is consistent with other studies showing increased noradrenergic activity in PTSD.

Adrenergic alpha-Agonists↗

Audit of antipsychotic prescribing in a private psychiatric hospital.

OBJECTIVES: There exists a substantial and growing body of evidence suggesting that antipsychotic medications are efficacious in the treatment of many non-psychotic psychiatric disorders. Although indications for the use of antipsychotics (particularly the atypicals) remain relatively narrow in Australia, psychiatrists seem to be using them for an expanding range of disorders in a variety of clinical settings. This has raised issues of cost-effectiveness and methods of funding of these medications. The present study aimed to quantify and describe the patterns of prescribing of antipsychotic medications in a large private psychiatric hospital. Another aim was to compare the findings with other published evidence, and consider the implications of antipsychotic use for current clinical practice in Australia. METHODS: A retrospective review of the medical records of 100 consecutive patients admitted to a private psychiatric hospital was conducted. The data collected included demographic details, major psychiatric diagnoses, all medications prescribed during the admission and their doses and, in the case of antipsychotics, the target symptoms/conditions for which they were prescribed. RESULTS: Fifty-nine per cent of inpatients received at least one dose of an antipsychotic during their admission. While all patients with psychotic illnesses were treated with antipsychotics, 57% of patients with primary mood disorders and 40% of patients with a primary anxiety disorder also received an antipsychotic. The most common indications for use of antipsychotics included the treatment of psychotic symptoms, augmentation of antidepressants, relief of anxiety symptoms and lessening of agitation, and control of difficult behaviours (including self-harm and aggression) associated with personality disorders. The most frequently used antipsychotic was olanzapine (22%), followed by chlorpromazine (20%), and quetiapine (14%). Eleven per cent of patients received a combination of two antipsychotics. CONCLUSIONS: Antipsychotic medications were widely used in a private psychiatric inpatient setting for the treatment of non-psychotic disorders. This finding parallels those from other Australian studies of psychotropic prescribing patterns. The issues of clinical utility, cost-effectiveness and benefits of funding of these medications for such wider indications require further study and evaluation.

Adolescent↗

Improving collaboration between private psychiatrists, the public mental health sector and general practitioners: evaluation of the Partnership Project.

OBJECTIVES: We describe the evaluation of the Partnership Project, which was designed to improve linkages between public and private sector mental health services. We consider the Project's key elements: a Linkage Unit, designed to improve collaborative arrangements for consumers and promote systems-level and cultural change; and the expansion of private psychiatrists' roles to include supervision and training, case conferencing and secondary consultation. The evaluation aimed to describe the impacts and outcomes of these elements. METHOD: The evaluation used de-identified data from the Linkage Unit database, the Project's billing system, and the Health Insurance Commission (HIC). It drew on consultations with key stakeholders (semistructured interviews with 36 key informants, and information from a forum attended by over 40 carers and a meeting of five public sector and three private sector psychiatrists) and a series of case studies. RESULTS: The Linkage Unit facilitated 224 episodes of collaborative care, many of which had positive outcomes for providers, consumers and carers. It had a significant impact at a systems level, raising consciousness about collaboration and influencing procedural changes. Thirty-two private psychiatrists consented to undertaking expanded roles, and the Project was billed $78 032 accordingly. Supervision and training were most common, involving 16 psychiatrists and accounting for approximately 80% of the total hours and cost. Commonwealth expenditure on private psychiatrists' participation in the expanded roles was not associated with a reduction in benefits paid by the HIC. Key informants were generally positive about the expanded roles. CONCLUSIONS: The Project represented a considered, innovative approach to dealing with poor collaboration between the public mental health sector, private psychiatrists and GPs. The Linkage Unit achieved significant systems-level and cultural change, which has the potential to be sustained. Expanded roles for private psychiatrists, particularly supervision and training, may improve collaboration, and warrant further exploration in terms of costs and benefits.

Adult↗

The emerging role of pharmacogenetics: implications for clinical psychiatry.

OBJECTIVE: This article aims to review the implications of pharmacogenetics for clinical psychiatry; these are discussed in the context of environmental and sociocultural factors. METHOD: A selective literature review was conducted using Medline search and other relevant references available to the authors. RESULTS: The individual differences in therapeutic and adverse effects of psychotropic drugs are largely determined by genetic factors. Recent advances in pharmacogenetics have highlighted the potential utility in predicting metabolic phenotypes, risks for side-effects and likelihood of drug response for the individual patient. CONCLUSIONS: Genotyping, especially for drug metabolizing enzymes, could enable more rational, cost-effective and optimal prescribing in future psychopharmacotherapy. Although the advances of pharmacogenetics may have many benefits in clinical practice, the importance of non-genetic factors must also be considered as cultural and environmental factors significantly impinge on response to medications. To clarify the extent pharmacogenetics can be adopted in clinical practice to predict drug response in patients from diverse backgrounds, further studies in different ethnic groups and clinical settings are required.

Cost-Benefit Analysis↗

Blunted prolactin response to D-fenfluramine in post-stroke major depression.

BACKGROUND: This study investigated whether patients suffering from post-stroke depressive disorder had a similar disturbance in central serotonergic function to that described in non-brain injured depressed patients. METHODS: Twenty-three depressed patients (nine major, 14 minor) and 38 non-depressed patients were examined 4-8 weeks post-stroke with a structured interview, rating scales and MRI brain scans. Patients were administered 30 mg D-fenfluramine orally and plasma prolactin and D-fenfluramine concentrations were measured for 6 h post-dose. RESULTS: The prolactin response was significantly blunted in major depression compared to minor depression and non-depressed patients as measured by both delta prolactin and area under the prolactin versus time curve. There was no significant relationship between prolactin response and lesion lateralization or any of the measured clinical characteristics. LIMITATIONS: The major limitation of the study is the relatively small number in each depressive group. CONCLUSIONS: Patients suffering from major depression in the post-stroke period have a blunted prolactin response to D-fenfluramine. This indicates a serotonergic abnormality consistent with that found in major depression where neurological disease is not present.

Aged↗

The association between depression and isotretinoin use in acne.

OBJECTIVE: The association between isotretinoin and depression has received little attention in the psychiatric literature despite an increasing number of reports in medical journals. The purpose of this paper is to highlight this association, examine the possible link and review the clinical implications. METHOD: A critical review of the literature pertaining to depression in patients with acne who were treated with isotretinoin was conducted. RESULTS AND CONCLUSIONS: The causal relationship between isotretinoin therapy and depression has not been clearly established and needs further study. Isotretinoin is likely to have a positive psychological impact for the majority of patients who benefit from such a highly efficacious anti-acne treatment. However, it is important to recognize that depression can occur as an idiosyncratic side-effect that requires urgent and appropriate treatment. Therefore, having a low threshold for detection of this uncommon complication and early psychiatric referral to address both the depression and its contributing factors may prevent serious consequences.

Acne Vulgaris↗

Is late onset depression a prodrome to dementia?

BACKGROUND: Recent research suggests there are clinical and biological differences between late onset depression (LOD) and early-onset depression (EOD). OBJECTIVES: In this paper we review clinical, epidemiological, structural neuroimaging and genetic investigations of late life depression that have been performed over the past two decades and offer evidence that LOD is often a prodromal disorder for dementia. RESULTS: LOD patients are more likely to have cognitive impairment and to have more deep white matter lesions (DWMLs). Evidence concerning cortical and temporal lobe atrophy is conflicting, while the ApoE 4 allele is not associated with LOD. CONCLUSIONS: It is likely that LOD is not a prodrome for a particular type of dementia, but the majority of patients who do develop dementia will acquire Alzheimer's disease (AD) or a vascular dementia, as these are by far the most common causes of dementia. This issue requires further clarification with follow-up of patients over the long term.

Age of Onset↗

Prospective study of depressive symptoms and quality of life in acne vulgaris patients treated with isotretinoin compared to antibiotic and topical therapy.

There have been recent concerns about the possible association between isotretinoin therapy and depressive symptoms. We conducted a prospective study to evaluate depressive symptoms and quality of life in acne patients having either isotretinoin or antibiotics/topical treatments. There were 215 patients (mean age 20 years) included in the study. Depression, quality of life and acne severity ratings were administered at baseline, 1 month, 3 months and end of treatment or 6 months, and compared between both treatment groups. The changes in the mean depression scores did not differ significantly between both groups (P = 0.62). The incidence of isotretinoin patients with moderate depressive symptoms remained relatively unchanged from baseline. The changes in the quality-of-life measures scores between treatment groups showed no significant difference. No correlation between isotretinoin dose and depression score was found. Although five isotretinoin patients were withdrawn during the study because of worsening of mood, no definite causal relationship was established. This pilot study does not appear to support any direct link between depression and isotretinoin, apart from being a rare unpredictable idiosyncratic side-effect. However, because of the study limitations, a larger study is needed to confirm the findings.

Acne Vulgaris↗

A case of mania induced by hypericum.

We report a case of mania induced by high doses of Hypericum perforatum in a 28-year-old depressed woman with no past history of mania or hypomania and no concomitant use of antidepressants.

Adult↗

Public and private psychiatry: can they work together and is it worth the effort?

OBJECTIVE: Partnerships in mental health care, particularly between public and private psychiatric services, are being increasingly recognized as important for optimizing patient management and the efficient organization of services. However, public sector mental health services and private psychiatrists do not always work well together and there seem to be a number of barriers to effective collaboration. This study set out to investigate the extent of collaborative 'shared care' arrangements between a public mental health service and private psychiatrists practising nearby. It also examined possible barriers to collaboration and some possible solutions to the identified problems. METHOD: A questionnaire examining the above factors was sent to all public sector mental health clinicians and all private psychiatrists in the area. RESULTS: One hundred and five of the 154 (68.2%) public sector clinicians and 103 of the 194 (53.1%) private psychiatrists returned surveys. The main barriers to successful collaboration identified by members of both sectors were: 'Difficulty communicating' endorsed by 71.4% of public clinicians and 72% of private psychiatrists, 'Confusion of roles and responsibilities' endorsed by 62.9% and 66%, respectively, and 'Different treatment approach' by 47.6% and 45.6%, respectively. Over 60% of private psychiatrists identified problems with access to the public system as a barrier to successful shared care arrangements. It also emerged, as hypothesized, that the public and private systems tend to manage different patient populations and that public clinicians in particular are not fully aware of the private psychiatrists' range of expertise. This would result in fewer referrals for shared care across the sectors. CONCLUSIONS: A number of barriers to public sector clinicians and private psychiatrists collaborating in shared care arrangements were identified. The two groups surveyed identified similar barriers. Some of these can potentially be addressed by changes to service systems. Others require cultural shifts in both sectors. Improved communications including more opportunities for formal and informal meetings between people working in the two sectors would be likely to improve the understanding of the complementary sector's perspective and practice. Further changes would be expected to require careful work between the sectors on training, employment and practice protocols and initiatives, to allow better use of the existing services and resources.

Attitude of Health Personnel↗