Barriers to the management of sexual dysfunction among people with psychosis: analysis of qualitative data from the REMEDY trial.

BACKGROUND: More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial. METHODS: We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis. RESULTS: Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients' mental stability, mutual discomfort and embarrassment about discussing a "taboo" subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these "hidden" side effects. CONCLUSION: The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891.

Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review.

INTRODUCTION: Sexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. AIM: To synthesize and analyze the evidence on management of antipsychotic-related sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporated in studies over the past decade. METHODS: EMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline. MAIN OUTCOME MEASURE: The primary outcome measure was any change in sexual function. RESULTS: 6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction. CLINICAL IMPLICATIONS: Due to the lack of high-quality data, no clinical recommendations can be made. STRENGTHS & LIMITATIONS: A comprehensive search strategy was used with an extensive number of relevant search terms including "erectile dysfunction" and newer antipsychotics such as aripiprazole. In light of evidence that prolactin is not a reliable marker for sexual dysfunction, this review focused its inclusion criteria on participants presenting with sexual dysfunction rather than with hyperprolactinemia, which should give its recommendations more validity. However, only 6 RCTs were identified, and results were overall limited by small sample size, brief treatment duration, and the potential for bias. CONCLUSION: Our findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia. Allen K, Baban A, Munjiza J, et al. Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review. J Sex Med 2019;16:1978-1987.

Lasting personality pathology following exposure to severe trauma in adulthood: retrospective cohort study.

BACKGROUND: Early exposure to trauma is a known risk factor for personality disorder (PD), but evidence for late-onset personality pathology following trauma in adults is much less clear. We set out to investigate whether exposure to war trauma can lead to lasting personality pathology in adults and to compare the mental health and social functioning of people with late-onset personality problems with those with PD. METHODS: We recruited patients who scored positively on the International Personality Disorder Examination (IPDE) in southern Croatia 15 years after the Croatian war of independence and used a semi-structured interview to establish when the person's personality-related problems arose. All participants also completed Harvard Trauma Questionnaire, and measures of mental health and social functioning. RESULTS: Among 182 participants with probable personality disorder, 65 (35.7%) reported that these problems started after exposure to war-trauma as adults. The most prevalent personality problems among those with late-onset pathology were borderline, avoidant, schizotypal, schizoid and paranoid. Participants with late-onset personality pathology were more likely to have schizotypal (75.4% vs. 47.3%) and schizoid traits (73.8% vs. 41.1%) compared to those with PD. Participants with late-onset personality pathology were three times more likely to have complex personality pathology across all three DSM-IV clusters compared to those with PD (OR = 2.96, 95% CI 1.54 to 5.67) after adjusted for gender and marital status. The prevalence of depression and social dysfunction were as high among those with late-onset personality pathology as among those with personality disorder. CONCLUSION: Retrospective accounts of people with significant personality pathology indicate that some develop these problems following exposure to severe trauma in adulthood. Personality-related problems which start in adulthood may be as severe as those that have an earlier onset. These findings highlight the long term impact of war trauma on the mental health and have implications for the way that personality pathology is classified and treated.

Severe war-related trauma and personality pathology: a case-control study.

BACKGROUND: Exposure to war-related trauma has long been recognised to have an adverse effect on mental health. We attempted to investigate whether people who have clinically significant personality-related problems 15 years after a war are more likely to have been exposed to severe war-related trauma than those who do not have significant personality difficulties. METHODS: A case -control study was conducted in southern Croatia, fifteen years after the 1991-1995 war. We recruited 268 participants: 182 cases who scored positively on the International Personality Disorder Examination scale (IPDE), and 86 controls who were IPDE negative. Severity of war-related trauma was assessed according to the 17 items on the Harvard Trauma Questionnaire (HTQ) trauma event scale, which were considered to be of severe (catastrophic) nature based on the ICD-10 description of catastrophic trauma and the opinion of trauma experts. All participants also completed measures of mental health (depression, anxiety and PTSD), social functioning and current substance misuse. RESULTS: Cases (IPDE positive) were eight times more likely to report exposure to severe war-related trauma than controls. This association increased after adjustments for demographic factors (OR = 10.1, 95% CI 5.0 to 20.4). The types of severe trauma most frequently reported were either the participants'own life being in direct danger or witnessing extreme violence inflicted on others or the result of violence towards others (murder, torture, seeing burned or disfigured bodies). Prevalences of depression, anxiety and PTSD were high among IPDE positive participants 15 years after exposure to war trauma. Their level of interpersonal dysfunction was considerably higher than that in controls (OR = 10.39, 95% CI 3.51 to 30.75). Alcohol consumption in cases was significantly higher with a mean of 14.24 units per week (sd = 11.03) when compared to controls whose mean number of alcohol units was 9.24 (sd = 7.25), t (73) = 2.16, p < 0.05, mean difference 4.99 (95% CI = 0.39 to 9.60). Similarly, a significantly higher number of cases reported current substance misuse (8.2% vs. 0.0%) X2 (1, n = 268) = 7.51, p < 0.05). CONCLUSION: Exposure to severe war-related trauma is a risk factor for interpersonal dysfunction15 years after people were exposed to an armed conflict. These findings have implications for assessing and meeting the long-term mental health needs of people in war-affected regions. Further research needs to be done to increase our understanding about the relationship between severe war trauma and personality related problems.

Interventions to improve the sleep quality of adults with personality disorder: A systematic review.

Poor quality sleep is common for people who have a diagnosis of personality disorder (PD). Core cognitive and behavioral features of PD may cause and perpetuate poor sleep, but to date, no review has collated the evidence on the efficacy of interventions to improve sleep quality for people with PD. Structured searches for interventional studies among adults with PD and reporting validated measures of sleep quality were conducted up to November 2022 in multiple databases. Single-case reports were excluded. Study quality was assessed with standardized risk of bias tools. Unreported data was sought systematically from authors. This review was pre-registered with an international prospective register of systematic reviews (PROSPERO) (CRD42021282105). Of the 3503 identified studies, nine met inclusion criteria, representing a range of psychological, pharmaceutical, and other interventions and outcome measures. Meta-analytic methods were not feasible because of the serious risk of bias in all studies, and results were therefore synthesized narratively. There is limited and low-quality evidence of the effects of a variety of interventions to improve the sleep quality of people living with PD. Further research might consider specifically including people diagnosed with PD in trials of sleep interventions and using sleep outcome measures in trials of established PD treatments.

The Relationship Between Antipsychotic-Induced Akathisia and Suicidal Behaviour: A Systematic Review.

OBJECTIVE: We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area. METHODS: Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting. RESULTS: Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies. CONCLUSION: The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.

Switching antipsychotic medication to reduce sexual dysfunction in people with psychosis: the REMEDY RCT.

BACKGROUND: Sexual dysfunction is common among people who are prescribed antipsychotic medication for psychosis. Sexual dysfunction can impair quality of life and reduce treatment adherence. Switching antipsychotic medication may help, but the clinical effectiveness and cost-effectiveness of this approach is unclear. OBJECTIVE: To examine whether or not switching antipsychotic medication provides a clinically effective and cost-effective method to reduce sexual dysfunction in people with psychosis. DESIGN: A two-arm, researcher-blind, pilot randomised trial with a parallel qualitative study and an internal pilot phase. Study participants were randomised to enhanced standard care plus a switch of antipsychotic medication or enhanced standard care alone in a 1 : 1 ratio. Randomisation was via an independent and remote web-based service using dynamic adaptive allocation, stratified by age, gender, Trust and relationship status. SETTING: NHS secondary care mental health services in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, have schizophrenia or related psychoses and experience sexual dysfunction associated with the use of antipsychotic medication. We recruited only people for whom reduction in medication dosage was ineffective or inappropriate. We excluded those who were acutely unwell, had had a change in antipsychotic medication in the last 6 weeks, were currently prescribed clozapine or whose sexual dysfunction was believed to be due to a coexisting physical or mental disorder. INTERVENTIONS: Switching to an equivalent dose of one of three antipsychotic medications that are considered to have a relatively low propensity for sexual side effects (i.e. quetiapine, aripiprazole or olanzapine). All participants were offered brief psychoeducation and support to discuss their sexual health and functioning. MAIN OUTCOME MEASURES: The primary outcome was patient-reported sexual dysfunction, measured using the Arizona Sexual Experience Scale. Secondary outcomes were researcher-rated sexual functioning, mental health, side effects of medication, health-related quality of life and service utilisation. Outcomes were assessed 3 and 6 months after randomisation. Qualitative data were collected from a purposive sample of patients and clinicians to explore barriers to recruitment. SAMPLE SIZE: Allowing for a 20% loss to follow-up, we needed to recruit 216 participants to have 90% power to detect a 3-point difference in total Arizona Sexual Experience Scale score (standard deviation 6.0 points) using a 0.05 significance level. RESULTS: The internal pilot was discontinued after 12 months because of low recruitment. Ninety-eight patients were referred to the study between 1 July 2018 and 30 June 2019, of whom 10 were randomised. Eight (80%) participants were followed up 3 months later. Barriers to referral and recruitment included staff apprehensions about discussing side effects, reluctance among patients to switch medication and reticence of both staff and patients to talk about sex. LIMITATIONS: Insufficient numbers of participants were recruited to examine the study hypotheses. CONCLUSIONS: It may not be possible to conduct a successful randomised trial of switching antipsychotic medication for sexual functioning in people with psychosis in the NHS at this time. FUTURE WORK: Research examining the acceptability and effectiveness of adjuvant phosphodiesterase inhibitors should be considered. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891. 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. 24, No. 44. See the NIHR Journals Library website for further project information.

Antipsychotic medications can improve the mental health of people with psychosis but may also cause side effects. These include sexual side effects, such as reduced desire for sex or less pleasure from having sex. One way to try to tackle this problem is to switch the medicine people take to one that is thought less likely to cause these problems. However, it is unclear if this helps, and switching medication could potentially harm mental health or cause new side effects. We conducted a study to compare the effect of switching with not switching the medication of people with psychosis experiencing sexual side effects. We collected information about sexual functioning, mental health, quality of life and use of services at the start of the study and 6 months later. We also interviewed nurses, doctors and patients to get their views about the study. We recruited 10 patients over a 12-month period and conducted interviews with 51 clinicians and four patients. Many clinicians said that they found it difficult to talk to their patients about sex. Some thought that these problems occurred rarely and that other side effects mattered more to patients. Many patients were concerned about switching their medication, especially when it had improved their mental health. Others felt that these side effects were not very important, and some were not prepared to take part in a trial that could delay a change being made to their medication. We did not collect enough information to be able to find out if switching medication helps people who experience sexual side effects of antipsychotic drugs. It is important that clinicians ask about sexual side effects of antipsychotic medication and that further efforts are made to find ways to help patients who experience them.

Development and Psychometric Properties of the Standardized Assessment of Severity of Personality Disorder (SASPD).

Personality disorder (PD) is increasingly categorized according to its severity, but there is no simple way to screen for severity according to ICD-11 criteria. We set out to develop the Standardized Assessment of Severity of Personality Disorder (SASPD). A total of 110 patients completed the SASPD together with a clinical assessment of the severity of personality disorder. We examined the predictive ability of the SASPD using the area under the ROC curve (AUC). Two to four weeks later, 43 patients repeated the SASPD to examine reliability. The SASPD had good predictive ability for determining mild (AUC = 0.86) and moderate (AUC = 0.84) PD at cut points of 8 and 10, respectively. Test-retest reliability of the SASPD was high (intraclass correlation coefficient = 0.93, 95% CI [0.88, 0.96]). The SASPD thus provides a simple, brief, and reliable indicator of the presence of mild or moderate PD according to ICD-11 criteria.

The Clinical Effectiveness and Cost-Effectiveness of Lamotrigine in Borderline Personality Disorder: A Randomized Placebo-Controlled Trial.

OBJECTIVE: The authors examined whether lamotrigine is a clinically effective and cost-effective treatment for people with borderline personality disorder. METHOD: This was a multicenter, double-blind, placebo-controlled randomized trial. Between July 2013 and November 2016, the authors recruited 276 people age 18 or over who met diagnostic criteria for borderline personality disorder. Individuals with coexisting bipolar affective disorder or psychosis, those already taking a mood stabilizer, and women at risk of pregnancy were excluded. A web-based randomization service was used to allocate participants randomly in a 1:1 ratio to receive either an inert placebo or up to 400 mg/day of lamotrigine. The primary outcome measure was score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. Secondary outcome measures included depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, and adverse events. RESULTS: A total of 195 (70.6%) participants were followed up at 52 weeks, at which point 49 (36%) of those in the lamotrigine group and 58 (42%) of those in the placebo group were taking study medication. The mean ZAN-BPD score was 11.3 (SD=6.6) among those in the lamotrigine group and 11.5 (SD=7.7) among those in the placebo group (adjusted difference in means=0.1, 95% CI=-1.8, 2.0). There was no evidence of any differences in secondary outcomes. Costs of direct care were similar in the two groups. CONCLUSIONS: The results suggest that treating people with borderline personality disorder with lamotrigine is not a clinically effective or cost-effective use of resources.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

Lasting personality pathology following exposure to catastrophic trauma in adults: systematic review.

BACKGROUND: By definition, personality disorders (PDs) are evident in late childhood and adolescence, but evidence for personality pathology occurring after adolescence is unclear. AIM: We aimed to review extant literature on personality change following exposure to catastrophic trauma in adults in order to identify the prevalence and clinical features of any long-term personality pathology. METHOD: Relevant studies were identified by searching three bibliographic databases (MEDLINE, EMBASE and PsychINFO) from inception to November 2011 using terms related to personality and trauma. RESULTS: No prospective studies that investigated long-term personality change following exposure to trauma in adults were found. Two retrospective studies reported the prevalence of enduring personality change of 2.6% and 6% (weighted prevalence 4.6%, 95% confidence interval 3.4-6.3%), and one study reported 20% increase in adult-onset antisocial behaviour following exposure to trauma. Findings from cross-sectional studies that examined the prevalence of PDs in people exposed to catastrophic trauma reported that Cluster C and Cluster A were the most common with avoidant, paranoid and obsessive-compulsive PDs among those most frequently reported. CONCLUSION: A minority of adults who are exposed to severe trauma appear to go on to develop significant personality pathology. The observed personality disturbance is multifarious and more extensive than the prototype described in ICD-10.