What clinicians need to know about intranasal esketamine for treatment-resistant depression?

OBJECTIVE: To review the usefulness of esketamine for treatment-resistant depression. METHOD: Pivotal trials of intranasal esketamine in treatment-resistant depression were synthesized as a narrative review. RESULTS: Esketamine is postulated to act through antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors, but opioidergic effects may also be involved. Unlike intravenous ketamine, esketamine is given intranasally (under clinical observation), usually in addition to an oral antidepressant. Trials compared esketamine plus antidepressant versus placebo plus antidepressant. At 4 weeks, remission was 37% higher with esketamine/antidepressant than placebo/antidepressant. Speed of response and improvement in suicidality were comparable. In stable remitters on esketamine/antidepressant, 45% relapsed when esketamine was withdrawn over the following 6 months (whereas 25% relapsed on esketamine/antidepressant). Response appears less likely in patients with multiple antidepressant failures. Adverse effects include dissociation, dizziness, nausea, sedation, and headache but no psychosis. Hypertension affected 13%, especially older patients. Dose frequency is twice-weekly for 4 weeks, then weekly/fortnightly thereafter. No abuse has been reported. Unsubsidised cost may be beyond the reach of many Australians. CONCLUSION: Intranasal esketamine plus antidepressant has been approved by regulators as moderately effective and acceptably tolerable for treatment-resistant depression. Cost is a drawback. Use often needs to be long-term and vigilance for abuse is essential.

Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of electroconvulsive therapy.

OBJECTIVES: To provide guidance for the optimal administration of electroconvulsive therapy, in particular maintaining the high efficacy of electroconvulsive therapy while minimising cognitive side-effects, based on scientific evidence and supplemented by expert clinical consensus. METHODS: Articles and information were sourced from existing guidelines and the published literature. Information was revised and discussed by members of the working group of the Royal Australian and New Zealand College of Psychiatrists' Section for Electroconvulsive Therapy and Neurostimulation, and findings were then formulated into consensus-based recommendations and guidance. The guidelines were subjected to rigorous successive consultation and external review within the Royal Australian and New Zealand College of Psychiatrists, involving the full Section for Electroconvulsive Therapy and Neurostimulation membership, and expert and clinical advisors and professional bodies with an interest in electroconvulsive therapy administration. RESULTS: The Royal Australian and New Zealand College of Psychiatrists' professional practice guidelines for the administration of electroconvulsive therapy provide up-to-date advice regarding the use of electroconvulsive therapy in clinical practice and are informed by evidence and clinical experience. The guidelines are intended for use by psychiatrists and also others with an interest in the administration of electroconvulsive therapy. The guidelines are not intended as a directive about clinical practice or instructions as to what must be done for a given patient, but provide guidance to facilitate best practice to help optimise outcomes for patients. The outcome is guidelines that strive to find the appropriate balance between promoting best evidence-based practice and acknowledging that electroconvulsive therapy is a continually evolving practice. CONCLUSION: The guidelines provide up-to-date advice for psychiatrists to promote optimal standards of electroconvulsive therapy practice.

The challenges facing the public mental health sector: implications of the Victorian Psychiatry workforce project.

OBJECTIVES: This paper reviews the major findings of the Victorian Psychiatry Attraction, Recruitment and Retention Needs Analysis Project and considers some of the implications for the psychiatrist workforce working in public sector psychiatry. CONCLUSIONS: The report provides a snapshot of the issues that are impairing the ability of Victorian psychiatrists to comprehensively treat those in our community who have severe mental illness. As the report shows, the issues impacting the profession are multi-faceted and complex, yet surmountable.

A Brief Measure for Assessing Patient Perceptions of Cognitive Side Effects After Electroconvulsive Therapy: The Subjective Assessment of Memory Impairment.

OBJECTIVES: Directly inquiring about patient experiences of memory problems after ECT may alert clinicians to the existence of treatment side effects and provide an impression of their intrusiveness. In this study, we examined use of a novel and brief patient-reported measure to assess perceptions of memory side effects and their functional consequences before and after an acute ECT treatment course. These outcomes were compared with objective cognitive and subjective quality of life measures. METHODS: Data for 75 patients who were prescribed an acute course of ECT were analyzed. Subjective and objective measures were assessed before ECT (pretreatment) and at posttreatment. Patient perceptions were assessed using the Subjective Assessment of Memory Impairment, which consists of two items: The Memory Problems item, and The Impact of Cognitive Adverse Events item. Objective cognitive outcomes were assessed using the Montreal Cognitive Assessment. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. RESULTS: Patient perceptions of their memory problems did not change across the ECT course, and their functional impact were considered less intrusive after ECT. Greater functional impact of memory impairment was related to poorer quality of life at posttreatment, but not at pretreatment. Subjectively rated cognitive functioning was not associated with objective cognitive outcomes. CONCLUSIONS: The Subjective Assessment of Memory Impairment is a brief tool for measuring patient-rated memory function. Overall, patients did not report any change in subjective memory problems after ECT. Although perceptions of functional memory impairment and quality of life were related after ECT, there was no association with objectively assessed cognitive outcomes.

Dissociative identity disorder (DID) in clinical practice - what you don't see may hurt you.

OBJECTIVES: To identify problems that interfere with the recognition, diagnosis and management of people with dissociative identity disorder (DID) presenting to psychiatric outpatient and inpatient services and suggest solutions. METHOD: Problems and suggested solutions associated with clinical presentations and management of people with DID are outlined with references to relevant literature. RESULTS: Problems in the recognition and management of DID are described. These lead to delays in diagnosis and costly, inappropriate management, destructive to services, staff and patients alike. Problems include lack of understanding and experience and scepticism about the disorder, resulting in failure to provide appropriate treatment.Some suggestions to improve recognition and management are included. CONCLUSION: Better recognition, diagnosis and management of DID will lead to better and more cost effective outcomes.

'Help us, she's fading away': How to manage the patient with anorexia nervosa.

BACKGROUND: Although integral to the early detection and treatment of anorexia nervosa, there is a paucity of clear guidance available for general practitioners (GPs). This paper attempts to bridge the gap between the specialist and generalist literature to assist the busy GP feel confident in identifying and managing these patients. OBJECTIVE: On reading this article it is anticipated the GP will feel well equipped to screen for and provide ongoing treatment to patients who pre-sent with eating disorders, particularly anorexia nervosa. This paper provides guidance for the identification and ongoing management of patients with anorexia nervosa, and supporting their carers. DISCUSSION: People affected by eating disorders, particularly anorexia nervosa, may deny having a problem, minimise their symptoms and resist treatment yet engage partially with their GP throughout the course of their illness. There are well-validated, quick screening tools that the non-specialist can use to identify patients at high risk of having an eating disorder.

Depression and anxiety.

Comorbid depression and anxiety disorders occur in up to 25% of general practice patients. About 85% of patients with depression have significant anxiety, and 90% of patients with anxiety disorder have depression. Symptomatology may initially seem vague and non-specific. A careful history and examination with relevant investigations should be used to make the diagnosis. Once the diagnosis is made, rating scales may identify illness severity and help in monitoring treatment progress. Both the depression disorder and the specific anxiety disorder require appropriate treatment. Psychological therapies, such as cognitive behaviour therapy, and antidepressants, occasionally augmented with antipsychotics, have proven benefit for treating both depression and anxiety. Benzodiazepines may help alleviate insomnia and anxiety but not depression. They have dependency and withdrawal issues for some people, and may increase the risk of falls in older people. Despite the availability of treatments, 40% of patients with depression or anxiety do not seek treatment, and of those who do, less than half are offered beneficial treatment.

Pharmacological approaches to the management of schizophrenia: 10 years on.

OBJECTIVE: To review the contemporary landscape regarding pharmacological treatments for schizophrenia. METHOD: Selective literature review. RESULTS: Newer antipsychotic agents include aripiprazole, asenapine, paliperidone, sertindole and ziprasidone. Each has some particular benefits and some shortcomings. Overall treatment efficacy (for positive symptoms at least) has not advanced substantially but some newer agents might have a better profile than older typical agents for negative and cognitive symptoms. Metabolic side effects and hyperprolactinaemia remain a problem with some of the newer agents and appropriate monitoring is required. CONCLUSIONS: Whilst newer antipsychotics have been welcome additions to our pharmacological armamentarium, mostly in terms of tolerability, we have still not seen a 'quantum leap' agent brought to market. Mechanisms of action apart from post-synaptic dopamine blockade appear worthy of further investigation in this regard.

A consensus statement for safety monitoring guidelines of treatments for major depressive disorder.

OBJECTIVE: This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring. METHOD: Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content. RESULTS: Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment. CONCLUSION: The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.

STAR*D: has it taught us anything about the management of depression?

OBJECTIVE: The aim of this paper was to review the large US National Institute of Mental Health-sponsored depression intervention effectiveness study, STAR*D, in order to evaluate critically its relevance for Australasian clinicians. CONCLUSIONS: STAR*D is a landmark study which tried to address issues of effectiveness rather than efficacy, of a number of interventions for depression. However, methodological shortcomings limit the utility of the study in informing Australasian clinical practice.

Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: a post hoc analysis.

OBJECTIVE: Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression. METHODS: This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20. RESULTS: Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated. CONCLUSIONS: These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.

Bipolar disorder: diagnostic issues.

Bipolar disorders are cyclical mood disorders with clinical features including distinct sustained periods of mood elevation. Briefer (4 days or more), mild episodes of mood elevation define bipolar II disorder; lengthier (7 days or more), more severe episodes (or those requiring hospitalisation), with or without psychotic features, define bipolar I disorder. Depressive periods are more common and lengthier than manic or hypomanic states, and are the main cause of disability. Bipolar depression may respond poorly to antidepressants and these medications may destabilise the illness. The diagnosis of bipolar disorder should be considered when a patient with depression is treatment resistant. Irritability is a common symptom in bipolar disorder, particularly during mixed states (during which patients have features of mood elevation and depression concurrently) or when there is rapid cycling of mood (more than four episodes of mood disorder per year). Alcohol misuse and use of illicit drugs may simulate mood changes in bipolar disorder. Accurate diagnosis and assessment of bipolar disorder is essential for clinical decision making and determining prognosis and treatments.

Antipsychotic use in the elderly: what doctors say they do, and what they do.

OBJECTIVE: To review psychiatrists' attitudes and actual practice on the use of typical and atypical antipsychotics in the elderly. METHODS: Audit data were collected from 18-old-age psychiatry units across Australia. The attitudes of old age psychiatrists and their perceptions of the efficacy, tolerability and clinical usefulness of antipsychotics were examined. RESULTS: The medications used for 321 patients were audited, and the attitudes of the 57 prescribing doctors were assessed. All available atypicals were prescribed and reported as more efficacious and clinically useful than typicals. Adverse events perceived by doctors as an obstacle to prescribing were more frequent than reported adverse event rates in product information. All diagnostic groups improved. Off-label use comprised almost 22% in this sample. CONCLUSIONS: Adverse events are impediments to prescribing, more so with typical than atypical antipsychotics. All available atypicals were used and appeared effective in this elderly population.

Beyond the evidence: is there a place for antidepressant combinations in the pharmacotherapy of depression?

Up to 45% of patients with debilitating and potentially lethal depressive illness do not achieve remission with initial drug treatment. Using combinations of antidepressants as an early option for treatment-resistant depression has become increasingly common. Before trying combination therapy, it is essential first to ensure diagnosis is correct, and then to optimise antidepressant monotherapy, using an effective dose for an adequate period. Subsequently, augmentation of antidepressants with lithium and triiodothyronine should be considered, as these strategies are strongly supported by numerous clinical trials. Electroconvulsive therapy is the most effective treatment for severe depression. There is little evidence to support use of antidepressant combinations. Risk of toxicity and drug interactions mandate that combinations be used as a last resort, and only in specialist settings.

Seizure threshold determination for electroconvulsive therapy: stimulus dose titration versus age-based estimations.

OBJECTIVE: This study compared electroconvulsive therapy (ECT) seizure threshold determined by stimulus dose titration with age-based estimations. METHOD: Patients with major depressive disorder had their initial seizure thresholds determined by stimulus dose titration and the results compared with age-based estimations. There are no significant differences in thresholds determined by these methods. RESULTS: Two hundred and three psychiatric patients (149 females, 54 males) had their seizure thresholds determined by stimulus dose titration. There was a significant positive correlation between seizure thresholds and age for males and females with male thresholds greater than female thresholds. Age determinations of seizure threshold would have resulted in excessive initial treatment stimuli for 30% of females and 8% of males. Ineffective stimulus doses would have been given to 2% of females and 7% of males on a full age basis and 64% using a half age strategy. CONCLUSIONS: For effective high-dose right unilateral ECT, initial seizure threshold should be determined by stimulus dose titration.

Dissociative disorders: pathways to diagnosis, clinician attitudes and their impact.

OBJECTIVES: To study the attitudes and experiences of Australian clinicians with dissociative disorders and the paths to diagnosis and experiences of patients. METHOD: The attitudes of Australian clinicians to dissociative disorders and the experiences of patients were assessed by questionnaires. The clinicians were mental health specialists and a small number of general medical practitioners. The patients had all been diagnosed with a dissociative disorder. RESULTS: Of the 250 clinicians, 21% reported experience with more than six cases on average of any one of the dissociative disorders, 38% with less than six, 42% with none; 55% regarded them as valid diagnoses, 35% dubiously valid and 10% invalid. Of the 55 patients, 76% reported delays in diagnosis (57%, >3 years and 25%, >10 years) with adverse consequences in 64%; 80% had experienced sceptical or antagonistic attitudes from clinicians, rated as destructive by 48%. They were disabled (60% rated as >50% impaired) and were heavy consumers of health services (48% hospitalized, 68% >5 times). There was considerable comorbidity including moderate or severe depression (96%), self-harm (68%), suicide attempts (69%), panic disorder (53%), eating disorders (75%), substance abuse (25%), poor physical health (44%), major interpersonal (70%) and sexual problems (90%). Patients rated individual psychotherapy as the most helpful treatment (90%) but medications, such as antidepressants, were also valued (60%). CONCLUSIONS: Although over half of the responding Australian clinicians thought that dissociative disorders were valid, the rest were dubious about their validity with 10% believing them to be invalid. Only 21% had considerable experience with the disorders. These findings may relate to some of the difficulties perceived by patients, which included delays in diagnosis, suboptimal treatment and negative experiences with clinicians.

Clinical characteristics and management of bipolar disorder in women across the life span.

Though prevalent in both genders, specific consideration needs to be given when treating a woman suffering from bipolar disorder over her lifetime. Bipolar disorder is a serious and incapacitating illness affecting an estimated 5% of women. The first episode of illness in women is usually a depressive episode. Female gender has been associated with greater axis-one comorbidity, more depressive episodes, rapid cycling and mixed affective states. Special consideration is required for the treatment of bipolar disorder during reproductive events. More studies are required to better understand the course, outcome and gender-specific treatment strategies of this disorder.