Olanzapine / fluoxetine combination for treatment resistant depression : efficacy and clinical utility

Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient’s personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery–Åsberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

A survey of combination antidepressant use in Australia

Objective: The aim of this study was to survey doctors working in psychiatry in Australia about the practice of using two antidepressants simultaneously.

Method: A postal survey was sent to all doctors in psychiatry in Australia enquiring about their prescribing history and their attitudes to combination antidepressants and related issues.

Results: Seventy-nine percent of respondents had used combination antidepressants. The most frequently reported combination was a selective serotonin reuptake inhibitor combined with a tricyclic antidepressant. Combinations of mirtazepine with venlafaxine and other antidepressants were the next most frequently used. Seventeen percent of respondents reported having seen a complication from combination antidepressants, 75% believed that Australian GPs should be given information on the use of combination antidepressants, 89% wished for more information on this topic, and 88% believed patients had a right to be informed of this option in their treatment. Use of combination antidepressants was more frequent than exceeding the recommended maximum dose of an individual antidepressant.

Conclusion: Combination antidepressants are used far more frequently in Australia than suspected previously. Research into safe and evidence-based practice is strongly indicated.

A pilot randomized, double-blind, placebo-controlled study of granisetron in the treatment of sexual dysfunction in women associated with antidepressant use

A pilot study was conducted to evaluate the usefulness of granisetron for the treatment of antidepressant induced sexual dysfunction in women. Twelve women with antidepressant induced sexual dysfunction (AISD) were assigned granisetron (n=5) or placebo (n=7) in a 14-day randomized, double-blind, placebo-controlled study. One participant in the granisetron group did not complete the study. Participants were assessed at baseline, day 7 and day 14 using the Feiger Sexual Function and Satisfaction Questionnaire and the Arizona Sexual Experience Scale. No statistical differences were measured at baseline or at endpoint between the granisetron or placebo group. This study did not produce evidence supporting the usefulness of granisetron in AISD.

'Mind and body' : a lifestyle programme for people on antipsychotic medication

Rationale Psychiatric illnesses such as schizophrenia and their treatments have consequences in terms of lifestyle, diet and weight.

Aims and objectives ‘Mind and Body’ is a 10-week programme of weekly sessions aimed to improve the health status of people treated with second generation antipsychotic medications.

Methods The programme focuses on a range of lifestyle strategies including diet and exercise and was conducted at a Community Health Centre by professionally qualified staff. Between 2002 and 2006, 50 participants enrolled in, and 30 completed the programme. Measures of body weight, health status (Short Form-36) and blood markets (plasma glucose, haemoglobin A1c and lipid profile) were collected at commencement and completion of the programme.

Results A modest improvement was demonstrated in mean values for the majority of measures collected.

Conclusions A lifestyle program for people treated with antipsychotic medications is achievable and may be worthwhile although gains may be modest.

Medication administration via enteral tubes : a survey of nurses' practices

Aim: This article is a report of a study examining the practices of acute care nurses when administering medication via enteral tubes. Background. Administering medication via enteral tubes is predominantly a nursing responsibility across countries. It is important to establish what nurses actually do when giving enteral medication to inform policy and continuing education development.

Method: In 2007, a survey was conducted using a random sample of acute care nurses at two large metropolitan hospitals in Melbourne, Australia. There were 181 Registered Nurses who participated in the study; 92 (50Æ8%) practised in intensive care units, 52 (28Æ7%) in surgical areas, 30 (16Æ6%) in medical areas and 7 (3Æ9%) were from combined medical–surgical areas. The questionnaire was developed by the researchers and a pilot study was conducted in August 2006 to test reliability, face validity and user-friendliness of the tool.

Results: Nurses reported using a range of methods to verify enteral tube position prior to administering enteral medication; some were unreliable methods. A majority reported administering enteric-coated and slow or extended release forms of medication, and giving solid forms of medication when liquid form was available. Nearly all (96%) reported flushing a tube after giving medication, 28% before, and 12% always flushed between each medication.

Conclusion: Enteral medication administration practices are inconsistent. Some nurses are using unsafe practices and may therefore compromise patient care.

Multifactorial influences on and deviations from medication administration safety and quality in the acute medical/surgical context

Background and Aims: Although numerous factors influence medication administration, our understanding of the interplay of these factors on medication quality and safety is limited. The aim of this study was to explore the multifactorial influences on medication quality and safety in the context of a single checking policy for medication administration in acute care.

Approach: An exploratory/descriptive study using non-participant observation and follow-up interview was used to identify factors influencing medication quality and safety in medication administration episodes (n = 30). Observations focused on nurses’ interactions with patients during medication administration, and the characteristics of the environment in which these took place. Confirmation of observed data occurred on completion of the observation period during short semi-structured interviews with participant nurses.

Findings: Findings showed nurses developed therapeutic relationships with patients in terms of assessing patients before administering medications and educating patients about drugs during medication administration. Nurses experienced more frequent distractions when medications were stored and prepared in a communal drug room according to ward design. Nurses deviated from best-practice guidelines during medication administration.

Implications: Nurses’ abilities and readiness to develop therapeutic relationships with patients increased medication quality and safety, thereby protecting patients from potential adverse events. Deviations from best-practice medication administration had the potential to decrease medication safety. System factors such as ward design determining medication storage areas can be readily addressed to minimise potential error.

Conclusions: Nurses displayed behaviours that increased medication administration quality and safety; however, violations of practice standards were observed. These findings will inform future intervention studies to improve medication quality and safety.

Effect of subjective reasoning and neurocognition on medication adherence for persons with schizophrenia

Objective: This study investigated the relationship between patients' reasoning about medication adherence and neurocognitive and clinical indices for a treatment-compliant sample of Japanese patients with schizophrenia.

Methods: Subjective reasoning about medication adherence was assessed by the Rating of Medication Influences (ROMI) scale. General intelligence, executive function, and verbal memory were assessed by the Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test, and Rey Auditory Verbal Learning Test, respectively.

Results: Higher prevention scores were associated with lower executive functioning and older age. Influence of others was associated with years of education, medication dosage, and IQ, and medication affinity was associated with education.

Conclusions: These results suggest that executive functioning, education, and general IQ may all be important factors in individual motivation for medication adherence.

Self-reported medication side effects in an older cohort living independently in the community - the Melbourne Longitudinal Study on Health Ageing (MELSHA) : cross-sectional analysis of prevalence and risk factors

Background Medication side effects are an important cause of morbidity, mortality and costs in older people. The aim of our study was to examine prevalence and risk factors for self-reported medication side effects in an older cohort living independently in the community.

Methods The Melbourne Longitudinal Study on Healthy Ageing (MELSHA), collected information on those aged 65 years or older living independently in the community and commenced in 1994. Data on medication side effects was collected from the baseline cohort (n = 1000) in face-to-face baseline interviews in 1994 and analysed as cross-sectional data. Risk factors examined were: socio-demographics, health status and medical conditions; medication use and health service factors. Analysis included univariate logistic regression to estimate unadjusted risk and multivariate logistic regression analysis to assess confounding and estimate adjusted risk.

Results Self-reported medication side effects were reported by approximately 6.7% (67/1000) of the entire baseline MELSHA cohort, and by 8.5% (65/761) of those on medication. Identified risk factors were increased education level, co-morbidities and health service factors including recency of visiting the pharmacist, attending younger doctors, and their doctor's awareness of their medications. The greatest increase in risk for medication side effects was associated with liver problems and their doctor's awareness of their medications. Aging and gender were not risk factors.

Conclusion Prevalence of self-reported medication side effects was comparable with that reported in adults attending General Practices in a primary care setting in Australia. The prevalence and identified risk factors provide further insight and opportunity to develop strategies to address the problem of medication side effects in older people living independently in the community setting.

Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction

Background: Contact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed-type hypersensitivity (DTH) reactions, affords immunity against tumor cells and microbes. CS response is a self-limiting reaction, and interleukin (IL)-10 is considered to be a natural suppressant of cutaneous inflammatory response. Recently, it has been demonstrated that major depression is related to activation of the inflammatory response and elevation of some parameters of cell-mediated immunity. It has been suggested that such activation of the immune system may play a role in etiology of depression. If this immunoactivation is involved in etiology of depression, one would expect that antidepressant agents may have negative immunoregulatory effects. To the best of our knowledge, the effect of antidepressants on contact hypersensitivity has not been studied.

Methods: The aim of the present study was to establish the effect of prolonged desipramine or fluoxetine treatment on CS reaction to picryl chloride.

Results: Antidepressants significantly suppressed CS reaction, fluoxetine by 53% whereas desipramine by 47% compared to positive control. Moreover, desipramine and fluoxetine decreased relative weight of auxillary lymph nodes. Desipramine decreased also relative weight of inguinal lymph nodes and spleens whereas desipramine and fluoxetine increased production of IL-10 in comparison to positive control.

Conclusion: The observed effect of antidepressant drugs on CS reaction is consistent with the hypothesis that T-cell mediated immunity is targeted by antidepressants.