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.

The integrative management of treatment-resistant depression: a comprehensive review and perspectives.

Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment.

Antidepressant mechanisms of deep brain stimulation for treatment resistant depression

Deep brain stimulation to clinically relevant brain targets all produced therapeutic responses in an animal model of antidepressant resistance. Such effects were achieved by modulating cellular stress, impaired synaptic plasticity, dysregulated dopamine transmission and energy metabolism. The implication of these findings underscore the need for using appropriate animal models to gain valuable insight on the neurobiological state of the organism in health and disease.

Cognitive remission: a novel objective for the treatment of major depression?

BACKGROUND: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD.

DISCUSSION: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

Feel blue? Touch green! Participation in forest/woodland management as a treatment for depression

Recent research by a team from Deakin University explored the health and wellbeing benefits of civic environmentalism – voluntary communal actions undertaken to promote ecosystem sustainability, typified by membership of a ‘friends of parks’ group. The research confirmed what was known intuitively: that belonging to such a group and undertaking the activities associated with such a group exposes people not only to the benefits of the natural environment, but also to other people and to opportunities to make a contribution which is socially valued.

On the basis of those findings, a pilot project involving intentional engagement of people suffering depression and related disorders in supported nature-based activities in a woodland environment is being implemented and evaluated. This article reports on that project and discusses the implications of its findings to date, and the findings of the three earlier projects, both for urban woodland/forest managers and for the health sector.

As this contribution indicates, there appears to be potential for the use of civic environmentalism to promote health, wellbeing and social connectedness for individuals and the wider population, as well as for groups with identified health vulnerabilities. However, the realization of the benefits of such an approach will be dependent on co-operation between the environment and health sectors to create and promote opportunities for increased civic environmentalism, and to identify and address the barriers to their effective use.

Satisfaction with general practitioner treatment of depression among residents of aged care facilities.

Objective: This article investigates consumer perspectives on the treatment for depression among older people in residential facilities. Method: Aged care residents who were aware of being treated for depression in the past 6 months (24 women and 7 men, mean age = 83 years) participated in an interview that assessed their perspective on treatments. Results: Although more than half of the participants in the sample reported overall satisfaction with the medical treatments received for depression, qualitative data provided indications of unsatisfactory service delivery, including perceptions of low treatment efficacy, short consultation times, the failure to assess affective symptomatology, and negative responses to residents’ disclosure of symptoms. Discussion: The findings are discussed in relation to previous research on consumer satisfaction with health services and issues that may be pertinent to the elderly depressed. Training for general practitioners providing treatment in aged care is indicated.

Treatment of depression in low-level residential care facilities for the elderly

Background: The rate of recognition and treatment of depressed older people in nursing homes is low. Data from the low-level residential care population have not been reported. This study aimed to collect information about the treatment of depression among older persons living in low-level residential care (hostels).

Method: The participants comprised 300 elderly residents from ten low-level residential care facilities from various suburbs in metropolitan Melbourne. The participants were interviewed by a trained clinical psychologist to determine the presence or absence of major or minor depressive disorder using the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). Each participant was also administered the Standardized Mini-mental State Examination (SMMSE) to determine level of cognitive function. The clinical psychologist then reviewed all cases in consultation with a geropsychiatrist experienced in the diagnosis of depression among older people, prior to assigning a diagnosis of depression.

Results: An important finding in this study was the low treatment for currently depressed residents, with less than half of those in the sample who were depressed receiving treatment. However, 61 of the 96 residents out of the sample of 300 who were on antidepressants were not currently depressed.

Conclusion: There is an under recognition and under treatment of currently depressed older people in low-level residential care facilities (hostels) just as has been reported in studies in nursing homes. However, there are high numbers receiving antidepressants who are not currently depressed.

An individualized psychosocial approach for "treatment resistant" behavioral symptoms of dementia among aged care residents

Background: Behavioral symptoms of dementia are common among residents in mainstream aged care settings, and have a substantial impact on residents and professional caregivers. This study evaluated the impact of individualized psychosocial interventions for behavioral symptoms through a small preliminary study.
Method: Interventions were delivered to a patient group of 31 psychogeriatric aged care residents who presented with behavioral symptoms of dementia that had failed to respond to pharmacological treatment approaches. Outcome data on severity of behaviors, health service utilization and staff burden of care were collected.
Results: A modest but significant reduction in staff ratings of the severity of aggressive and verbally agitated behavioral symptoms was found, with an associated reduction in their perceptions of the burden of caring for these patients. Reduced behavioral disturbance was associated with a reduction in the requirement for primary care consultations, and all participants were able to continue to reside in mainstream aged care facilities, despite an increase in the severity of dementia.
Conclusions: This study supported the use of individualized psychological strategies for behavioral symptoms at all stages of dementia. Methodological limitations of this preliminary study are discussed.