Patient perspectives of lithium and quetiapine augmentation treatment in treatment-resistant depression: A qualitative assessment.

BACKGROUND: Treatment-resistant depression (TRD) has a profound cost to patients and healthcare services worldwide. Pharmacological augmentation is one therapeutic option for TRD, with lithium and quetiapine currently recommended as first-line agents. Patient opinions about pharmacological augmentation may affect treatment outcomes, yet these have not been systematically explored. AIMS: This study aimed to qualitatively assess patient experiences of lithium and quetiapine augmentation. METHODS: Semi-structured interviews were conducted with 32 patients from the ongoing lithium versus quetiapine open-label trial comparing these augmentation agents in patients with TRD. Interviews were audio recorded, transcribed and a thematic analysis was used to assess patient opinions of each agent. RESULTS: Four main themes were generated from the thematic analysis: 'Initial concerns', 'Experience of side effects', 'Perception of treatment efficacy' and 'Positive perception of treatment monitoring'. Patient accounts indicated a predominantly positive experience of lithium and quetiapine augmentation. Greater apprehension about side effects was reported for lithium prior to treatment initiation, but greater experience of negative side effects was reported for quetiapine. Clinical monitoring was perceived positively. CONCLUSION: Patient accounts suggested treatment augmentation with lithium or quetiapine was acceptable and helpful for most patients. However, anticipation and experiences of adverse side effects may prevent some patients from benefitting from these treatments.

Cognitive-behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT.

BACKGROUND: Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive-behavioural therapy for adults with dissociative seizures. DESIGN: This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. SETTING: This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive-behavioural therapy services. PARTICIPANTS: Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. INTERVENTIONS: Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive-behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. MAIN OUTCOME MEASURES: The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. RESULTS: In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive-behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1-35 dissociative seizures); cognitive-behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0-20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive-behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7-12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect -0.39, 95% confidence interval -0.61 to -0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive-behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval -0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive-behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. LIMITATIONS: Unlike outcome assessors, participants and clinicians were not blinded to the interventions. CONCLUSIONS: There was no significant additional benefit of dissociative seizure-specific cognitive-behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive-behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive-behavioural therapy. FUTURE WORK: Examination of moderators and mediators of outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information.

Dissociative seizures resemble epileptic seizures or faints, but can be distinguished from them by trained doctors. Dissociation is the medical word for a 'trance-like' or 'switching off' state. People with dissociative seizures commonly have other psychological or physical problems. Quality of life may be low. The condition accounts for about one in every six patients seen in hospitals because of seizures. We wanted to find out if people with dissociative seizures receiving standardised treatment would also benefit from a talking therapy, called cognitive­behavioural therapy, made specific to this disorder. We did a randomised controlled trial to find out if people with dissociative seizures given standardised treatment and cognitive­behavioural therapy (talking therapy) would do better than those given standardised treatment alone. Standardised treatment of dissociative seizures began with careful diagnosis from a neurologist and then further assessment and treatment from a psychiatrist. In total, 368 people with dissociative seizures participated, with half receiving standardised treatment alone and half having talking therapy plus standardised treatment. We measured seizures and psychological and physical health in both trial groups. We also investigated whether or not cognitive­behavioural therapy was good value for money. After 12 months, patients in both trial groups seemed to have fewer monthly seizures, but there was no advantage in the talking therapy group. Patients in the talking therapy group had more consecutive days without seizures, reporting less impact from them in everyday situations. Patients in the talking therapy group, and their doctors, considered improvements to be better, and patients in this group reported greater satisfaction with treatment. However, the talking therapy was expensive and not as cost-effective as hoped. Interviews with patients and study clinicians showed that they valued aspects of both treatments and of the care provided by the multidisciplinary teams. Overall, cognitive­behavioural therapy designed for dissociative seizures plus standardised treatment was not better at reducing the total numbers of seizures reported, but did produce several positive benefits for participants compared with standardised treatment alone.

A retrospective examination of care pathways in individuals with treatment-resistant depression.

BACKGROUND: Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear. AIMS: To explore the extent and nature of 'treatment gaps' (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK. METHOD: Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced. RESULTS: Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment. CONCLUSIONS: There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.

The experiences of therapists providing cognitive behavioral therapy (CBT) for dissociative seizures in the CODES randomized controlled trial: A qualitative study.

OBJECTIVES: Little is known about the experiences of therapists delivering psychotherapy for patients with dissociative seizures (DS), a complex disorder associated with a range of comorbid psychosocial and mental health difficulties. This study set out to explore therapists' experiences of delivering DS-specific, manualized cognitive behavioral therapy (CBT) to adults with DS within the context of a randomized control trial. METHODS: Interviews were conducted with 12 therapists involved in the COgnitive behavioral therapy vs standardized medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial and were analyzed using thematic framework analysis (TFA). RESULTS: Six main themes emerged, namely 1) aspects of the intervention that were favored, while others were not always considered applicable; 2) multiple and complex difficulties faced by patients; 3) working effectively within the protocol; 4) limitations of the protocol; 5) significance of formulation; and 6) quality of standardized medical care (SMC) and difficulties of diagnosis delivery. These addressed valued aspects of the intervention, complexities of the patient group, and experiences working within a structured treatment protocol. Family involvement and psychoeducation were highlighted as important components; the applicability of graded exposure techniques, however, was restricted by patients' apparent emotional avoidance. The structure provided by the treatment protocol was valued, but flexibility was important to individualize treatment in complex cases. A comprehensive formulation was fundamental to this. The initial diagnostic explanation provided by neurologists and psychiatrists was generally considered beneficial, with patients often perceived to enter therapy with a better understanding of their condition. CONCLUSIONS: This study demonstrated that the DS-specific CBT intervention met with general approval from therapists who also highlighted some practical challenges. Because of the nature of the condition, the need for experience of working with complex patients should be considered when applying the intervention to individual cases. Setting the CBT intervention in the context of a structured care pathway involving neurology and psychiatry may facilitate the therapeutic process.