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Ketamine has recently received considerable attention regarding its antidepressant and anti-suicidal effects. Trials have generally focused on short-term effects of single intravenous infusions. Research on patient experiences is lacking.
To investigate the experiences over time of individuals receiving ketamine treatment in a routine clinic, including impacts on mood and suicidality.
Twelve fee-paying patients with treatment-resistant depression (6 females, 6 males, age 21–70 years; 11 reporting suicidality and 6 reporting self-harm) who were assessed as eligible for ketamine treatment participated in up to three semi-structured interviews: before treatment started, a few weeks into treatment and ≥2 months later. Data were analysed thematically.
Most participants hoped that ketamine would provide respite from their depression. Nearly all experienced improvement in mood following initial treatments, ranging from negligible to dramatic, and eight reported a reduction in suicidality. Improvements were transitory for most participants, although two experienced sustained consistent benefit and two had sustained but limited improvement. Some participants described hopelessness when treatment stopped working, paralleled by increased suicidal ideation for three participants. The transient nature and cost of treatment were problematic. Eleven participants experienced side-effects, which were significant for two participants. Suggestions for improving treatment included closer monitoring and adjunctive psychological therapy.
Ketamine treatment was generally experienced as effective in improving mood and reducing suicidal ideation in the short term, but the lack of longer-term benefit was challenging for participants, as was treatment cost. Informed consent procedures should refer to the possibilities of relapse and associated increased hopelessness and suicidality.
Only one-third of patients with major depressive disorder achieve remission. One new and promising treatment, ketamine, may prove challenging to implement because of its abuse potential. Although clinicians' views have been sought, we need patients' views before large scale roll-out is considered.
To explore patients’ and carers' views to inform policy and practical decisions about the clinical use of ketamine.
We carried out a mixed-methods study using data from 44 participants in 21 focus groups in three sessions and an online survey with patients, carers and advocates during a consultation day. Focus groups explored participant's views about ketamine as a form of treatment and the best way for ketamine to be prescribed and monitored. The qualitative data were analysed by two patient–researchers using an exploratory framework analysis and was supplemented by a survey.
The ten themes generated were monitoring, information, effect on daily life, side-effects, recreational use, effectiveness, appropriate support, cost, stigma and therapy. Participants wanted better evidence on the safety of ketamine after long-term use and felt that monitoring was required. Collecting this information would provide evidence for ketamine's safe use and administration. There were, however, concerns about the misuse of this information. Practical issues of access were important: repeated travelling to clinics and a lack of sufficiently informed medical staff were key barriers.
Clinicians have some similar and some different views to those of patients, carers and advocates, which need to be considered in any future roll-out of ketamine.
Declaration of interest
R.M. has had UK National Institute for Health Research grant funding to study ketamine, is participating in trials of esketamine, runs a clinic that provides ketamine treatment, and has consulted for Johnson & Johnson and Eleusis.
Ketamine and related compounds, such as esketamine, are of relevance to ECT practice for several reasons. First, as a drug with marked rapid antidepressant activity in people with treatment resistant depression (TRD), it may become an alternative to ECT in some cases. Second, ECT suites are a suitable setting for intravenous or other routes of directly observed therapy and ECT staff have experience with this patient group. Third, there may be synergy between ketamine and neuromodulatory therapies such as TMS.
Off-label ketamine treatment has shown acute antidepressant effects that offer hope for patients with therapy-resistant depression. However, its potential for integration into treatment algorithms is controversial, not least because the evidence base for maintenance treatment with repeated ketamine administration is currently weak. Ketamine is also a drug of misuse, which has raised concerns regarding the target population. Little is known about which patients would seek ketamine treatment if it were more widely available.
To explore some of the characteristics of the patients actively seeking ketamine treatment.
An online survey containing questions about duration of current depressive episode, number of antidepressants used and other comments was completed by patients who were exploring the internet regarding the possibility of ketamine for depression.
Of the 1088 people who registered their interest, 93.3% reported depression, 64.3% reported a chronic course of their symptoms and in the past 10 years, 86.3% had tried at least two antidepressants. Desperation was a common theme, but this appeared to be competently expressed. A small minority (<8%) reported experience of illegal ketamine use.
It cannot be ruled out that patients with different degrees of treatment resistance and comorbidities will seek treatment with ketamine. This stresses the urgency to perform larger randomised controlled trials as well as to systematically monitor outcomes and adverse effects of ketamine, that is currently prescribed off-label for patients in need.
Declaration of interest
R.M. is consulting and is Principal Investigator for Janssen trials of esketamine and is consulting for Eleusis.
The appeal of ketamine – in promptly ameliorating depressive symptoms even in those with non-response – has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives – derived from evidence and clinical experience – and to consider strategies for future investigations.
Considering the ample evidence of involvement of the glutamate system in the pathophysiology of depression, pre-clinical and clinical studies have been conducted to assess the antidepressant efficacy of glutamate inhibition, and glutamate receptor modulators in particular. This review focuses on the use of glutamate receptor modulators in unipolar depression.
There is emerging evidence that glutamatergic system dysfunction might play an important role in the pathophysiology of bipolar depression. This review focuses on the use of glutamate receptor modulators for depression in bipolar disorder.
The brevity of training and assessment for independent nurse prescribers has caused some concern. We aimed to validate an Objective Structured Clinical Examination (OSCE) for potential nurse prescribers in dementia. Nurses' performance after 12 days of training for potential prescribers was compared with that of doctors of different grades.
The performance of doctors, but not nurses, correlated with years of experience. Many nurses, especially those working in memory clinics, scored better than junior doctors.
This OSCE provides evidence of potential prescribers' competency for employers. This could make a significant contribution to maintaining high standards of patient safety with nurse prescribing. This may also be an appropriate addition to the assessment of specialty trainees as well as for revalidation.
The occurrence of episodes of getting lost was examined in 104 subjects with dementia who were assessed every 4 months over 5 years. All subjects were initially living at home with a caregiver who could give good information. Forty-three subjects needed to be brought back home at least once. Five subjects repeatedly got lost. Forty-six subjects were kept behind locked doors at some point. Subjects who got lost were more likely to become permanently resident in institutions (odds ratio = 7.3; 95% confidence interval: 3.0 to 17.8). Patients who performed better on a behavioral test of topographical memory were less likely to get lost over the subsequent 5 years (negative predictive value: 90%). The risk of patients with dementia getting lost is substantial and requires frequent intervention by caregivers. This risk is a major reason for institutionalization. A simple test may help in assessing the risk of getting lost in patients with dementia.
Objective: This article analyzes the natural history of wandering behavior throughout the course of dementia. Design: Prospective, 10-year, longitudinal study of wandering behavior in dementia, with autopsy follow-up. Setting: Participants with dementia, living at home with a carer. All lived in Oxfordshire, UK. Participants: Eighty-six people with dementia who were living at home with a carer and who were able to walk unaided at entry to study. Measures: At 4-monthly intervals, the carers were interviewed using the Present Behavioural Examination to assess wandering behavior were distinguished. Results: Changes in wandering behavior were not generally related to gender, age, or time since onset of dementia. Onset of different types of wandering behavior showed some relationship with cognitive state. Various forms of increased walking first appeared during moderate dementia, each type typically persisting for 1 to 2 years. Late dementia was characterized by decreased walking and immobility. Conclusions: Wandering behavior in dementia can cause great problems for carers. There are different causes for such changes, some of which are related to cognitive ability, for example increased confusion results in ineffectual “pottering” and getting lost. Increased walking at night corresponds with disruption of diurnal rhythm.
Syndromes are clusters of symptoms that tend to occur together in the same patient. They usually are described crosssectionally (i.e., the symptoms occur in the same individual at the same time) but can also occur longitudinally (i.e., the symptoms occur in the same individual but at different times).
Alzheimer's disease and other types of dementia are characterised by numerous psychiatric and behavioural changes. Little is known of their natural history.
To investigate the sequence and pattern of these changes throughout the course of dementia.
One hundred people, initially living at home with carers, entered a prospective, longitudinal study. At four-monthly intervals, behavioural and psychiatric symptoms were assessed using the Present Behavioural Examination and Mini-Mental State Examination. Follow-up continued for up to nine years (mean 3.3 years; s.d. 2.4). Patterns of onset and disappearance of these symptoms, their sequence and association with time of death and cognitive decline were analysed. Autopsy confirmed a diagnosis of pure Alzheimer's disease in 48 subjects. Data for this subgroup are presented.
Some changes tend to occur earlier than others but changes can occur at almost any time in the course of dementia.
The natural history of behaviour changes in Alzheimer's disease shows great individual variation although some changes tend to follow a recognisable sequence.
Psychiatric patients have had the right to see their notes from 1 November 1991. The ‘Access to Health Records Act (1990)’ makes provision for certain parts of the record to be exempt, including information which may cause serious mental or physical harm to the patient or anyone else. In addition, patients should not have access to information given by third party informants unless appropriate consent has been obtained. The legislation only applies to records made after 1 November 1991. It does not cover informal arrangements where written application for access is not made.
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