The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial.

BACKGROUND: Cognitive stimulation therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that home-based programmes of cognitive stimulation delivered by family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual cognitive stimulation therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (well-being) for the caregiver. METHODS AND FINDINGS: A single-blind, pragmatic randomised controlled trial (RCT) was conducted at eight study sites across the United Kingdom. The intervention and blinded assessment of outcomes were conducted in participants' homes. Three hundred fifty-six people with mild to moderate dementia and their caregivers were recruited from memory services and community mental health teams (CMHTs). Participants were randomly assigned to iCST (75, 30-min sessions) or treatment as usual (TAU) control over 25 wk. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher. Primary outcomes were cognition (Alzheimer's Disease Assessment Scale-cognitive [ADAS-Cog]) and self-reported QoL (Quality of Life Alzheimer's Disease [QoL-AD]) for the person with dementia and general health status (Short Form-12 health survey [SF-12]) for the caregiver. Secondary outcomes included quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationship Scale) and health-related QoL (European Quality of Life-5 Dimensions [EQ-5D]) for the caregiver. Intention to treat (ITT) analyses were conducted. At the post-test (26 wk), there were no differences between the iCST and TAU groups in the outcomes of cognition (mean difference [MD] = -0.55, 95% CI -2.00-0.90; p = 0.45) and self-reported QoL (MD = -0.02, 95% CI -1.22-0.82; p = 0.97) for people with dementia, or caregivers' general health status (MD = 0.13, 95% CI -1.65-1.91; p = 0.89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1.77, 95% CI 0.26-3.28; p = 0.02), and iCST improved QoL for caregivers (EQ-5D, MD = 0.06, 95% CI 0.02-0.10; p = 0.01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention. CONCLUSIONS: There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers' QoL. TRIAL REGISTRATION: The iCST trial is registered with the ISRCTN registry (identified ISRCTN 65945963, URL: DOI 10.1186/ISRCTN65945963).

The p-EVES study design and methodology: a randomised controlled trial to compare portable electronic vision enhancement systems (p-EVES) to optical magnifiers for near vision activities in visual impairment.

PURPOSE: To describe the study design and methodology for the p-EVES study, a trial designed to determine the effectiveness, cost-effectiveness and acceptability of portable Electronic Vision Enhancement System (p-EVES) devices and conventional optical low vision aids (LVAs) for near tasks in people with low vision. METHODS: The p-EVES study is a prospective two-arm randomised cross-over trial to test the hypothesis that, in comparison to optical LVAs, p-EVES can be: used for longer duration; used for a wider range of tasks than a single optical LVA and/or enable users to do tasks that they were not able to do with optical LVAs; allow faster performance of instrumental activities of daily living; and allow faster reading. A total of 100 adult participants with visual impairment are currently being recruited from Manchester Royal Eye Hospital and randomised into either Group 1 (receiving the two interventions A and B in the order AB), or Group 2 (receiving the two interventions in the order BA). Intervention A is a 2-month period with conventional optical LVAs and a p-EVES device, and intervention B is a 2-month period with conventional optical LVAs only. RESULTS: The study adopts a mixed methods approach encompassing a broad range of outcome measures. The results will be obtained from the following primary outcome measures: Manchester Low Vision Questionnaire, capturing device 'usage' data (which devices are used, number of times, for what purposes, and for how long) and the MNRead test, measuring threshold print size, critical print size, and acuity reserve in addition to reading speed at high (≈90%) contrast. Results will also be obtained from a series of secondary outcome measures which include: assessment of timed instrumental activities of daily living and a 'near vision' visual functioning questionnaire. A companion qualitative study will permit comparison of results on how, where, and under what circumstances, p-EVES devices and LVAs are used in daily life. A health economic evaluation will provide results on: the incremental cost-effectiveness of p-EVES compared to optical magnifiers; cost-effectiveness; and cost-utility. CONCLUSIONS: The evidence base in low vision rehabilitation is modest and further high quality clinical trials are required to inform decisions on healthcare provision. The p-EVES study findings are anticipated to contribute to this broader evidence requirement, with the methodological issues evident here being relevant to other trials within the field.

Life review and life story books for people with mild to moderate dementia: a randomised controlled trial.

OBJECTIVES: To evaluate the effect of different pathways for developing a life story book (LSB) for people with dementia. METHOD: Preliminary randomised control trial; 23 people with dementia in care homes (mean age 86) randomly assigned to receive either 12 individual life review sessions and co-creating a LSB or a personal LSB created by their relatives as a 'gift' RESULTS: No difference in quality of life (quality of life-Alzheimer's disease (QOL-AD)) was observed between the two groups, six weeks after having received the LSB (F(1,20) = 0.08, p = 0.77). At this point, QOL-AD had improved for both groups, but there was a significant between-group difference at an intermediate assessment immediately after the life review sessions had been completed, before the LSBs were received (F(1, 20) = 5.11, p = 0.035), in favour of life review. A similar pattern was observed on autobiographical memory (extended autobiographical memory interview), with the life review group improving significantly more than the gift group during the life review sessions, but no difference was observed once all participants had had their LSB for six weeks. After the LSBs were produced - by either pathway - quality of relationship as rated by relatives improved significantly (F(2, 39) = 19.37, p < 0.001) and staff knowledge regarding the resident and attitudes to dementia improved. CONCLUSION: The creation of LSBs - either through a life review process or by relatives without involving the person with dementia - has benefits for people with dementia, relatives and staff in care homes. However, undertaking a life review requires training and supervision.

Delay in discharge and its impact on unnecessary hospital bed occupancy.

BACKGROUND: Elderly patients are potentially more vulnerable to prolonged hospital stay as they frequently require additional resources to facilitate their discharge. In an acute hospital setting, we aimed to quantify and compare length of stay (LOS) for all patients over and under the age of 65, and identify the number and cause of days lost under the care of a single surgical unit. METHODS: Over a 4 month period from January to April 2010, data on the management and source of potential delay was collected daily on consecutive patients admitted and discharged under the care of one consultant surgeon at a district general hospital. Statistical analysis was then performed with particular focus on actual delays affecting elderly patients. RESULTS: A total of 99 complete inpatients episodes were recorded. There were 30 elective and 69 acute admissions. 10 (33%) elective vs. 42 (61%) acute patients encountered delays, losing 39 and 232 days respectively (χ2 [1, N = 99] = 6.36, p = .012). 23 of a total 39 elderly patients admitted acutely required specialist care of the elderly opinion and placement in community hospitals resulting in delays of 188 days. vs. 36 days for the 16 discharged home and 8 days for 30 patients under 65 (χ2 (2, N = 69) = 26.54, p = <.001). CONCLUSIONS: Elderly patients experiencing acute surgical admission and discharge to community hospitals had prolonged LOS due to significant delays associated with care of the elderly provision. The financial considerations behind bed capacity in primary and secondary care and the provision of care of elderly services need to be balanced against unnecessary occupancy of acute hospital beds with its associated health and economic implications.

Increasing pre-school children's consumption of fruit and vegetables. A modelling and rewards intervention.

Using a repeated measures design, in a nursery setting, a modelling and rewards intervention targeted preschool children's consumption of 8 fruit and 8 vegetables (presented as 4 different food sets, each comprising 2 fruit and 2 vegetables). During the 16-day Baseline 1, and subsequent baselines, the children received a different food set daily, first at snacktime and again at lunchtime; consumption of these foods was not rewarded. In the 32-day fruit intervention phase, Food Set 2 and Food Set 3 were presented on alternate days; rewards were presented only at snacktime, and only for consumption of the fruit components. Following Baseline 2 and Baseline 3, the intervention targeted snack consumption of the vegetable components of Food Sets 1 and 4. Finally, Baseline 4, and 6-month Follow up were conducted. The interventions produced large and significant increases in target fruit and vegetable consumption with smaller, but significant, increases for the paired, opposite category, non-target foods. Immediately after each intervention, increases based on within-category generalisation were also evident. All increases generalised strongly to the no-rewards lunchtime context. Contrary to theories predicting response decrements, the increases in preschoolers' fruit and vegetable consumption were maintained at Follow up, six months after rewards were withdrawn.

The extended school aged Incredible Years parent programme.

BACKGROUND: This paper reports on outcomes for the Incredible Years (IY) parent programme with parents of 8-13 year olds. METHOD: The sample consisted of 280 parents of children at risk of adolescent antisocial behaviour, mean age 10.3 years. RESULTS: Paired t tests for both the per protocol (t(113) = 8.41, p < .001) and intention-to-treat (t(258) = 7.37, p < .001) data found significant improvements in child behaviour problems (ECBI). Statistically significant improvements were also found for parental depression and parenting skills. CONCLUSIONS: The Incredible Years School Aged programme is effective in improving child behaviour, parenting competencies and parental mental health with parents of youngsters aged 8-13 years.

Staying well after depression: trial design and protocol.

BACKGROUND: Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. METHODS/DESIGN: This trial compares Mindfulness-Based Cognitive Therapy (MBCT), a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE), an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU). It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. DISCUSSION: This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent depression--that in people who become suicidal when depressed.

Who benefits and how does it work? Moderators and mediators of outcome in an effectiveness trial of a parenting intervention.

We examined mediators and moderators of change in conduct problems, in a multiagency randomized trial of the Incredible Years parenting program. Preschoolers (n = 153) at risk for conduct problems were randomly assigned to intervention (n = 104) and wait-list (n = 49) groups. Boys and younger children, and those with more depressed mothers, tended to show greater improvement in conduct problems post-intervention. Other risk factors (i.e., teen or single parenthood, very low income, high initial levels of problem behavior) showed no predictive effects, implying intervention was at least as successful at helping the most disadvantaged families, compared to more advantaged. Mediator analyses found change in positive parenting skill predicted change in conduct problems.

Long-term effectiveness of a parenting intervention for children at risk of developing conduct disorder.

BACKGROUND: The typical pattern for intervention outcome studies for conduct problems has been for effect sizes to dissipate over time with decreasing effects across subsequent follow-ups. AIMS: To establish whether the short-term positive effects of a parenting programme are sustained longer term. To observe trends, and costs, in health and social service use after intervention. METHOD: Parents with children aged 36-59 months at risk of developing conduct disorder (n = 104) received intervention between baseline and first follow-up (6 months after baseline n = 86) in 11 Sure Start areas in North Wales. Follow-ups two (n = 82) and three (n = 79) occurred 12 and 18 months after baseline. Child problem behaviour and parenting skills were assessed via parent self-report and direct observation in the home. RESULTS: The significant parent-reported improvements in primary measures of child behaviour, parent behaviour, parental stress and depression gained at follow-up one were maintained to follow-up three, as were improved observed child and parent behaviours. Overall, 63% of children made a minimum significant change (0.3 standard deviations) on the Eyberg Child Behavior Inventory problem scale between baseline and follow-up (using intention-to-treat data), 54% made a large change (0.8 standard deviations) and 39% made a very large change (1.5 standard deviations). Child contact with health and social services had reduced at follow-up three. CONCLUSIONS: Early parent-based intervention reduced child antisocial behaviour and benefits were maintained, with reduced reliance on health and social service provision, over time.

Positive- and negative peer modelling effects on young children's consumption of novel blue foods.

OBJECTIVE: The effects of positive- and negative peer modelling on children's consumption of a novel blue food, presented in each of four snack meals during an "activity" day, were evaluated. It was predicted that: (i) novel food consumption would increase after positive modelling, but decrease after negative modelling; (ii) modelling effects would generalise to a second novel blue food when participants were alone when they ate their snack; (iii) that positive modelling would reverse the effects of negative modelling. DESIGN: A mixed design was employed with random assignment to either Groups A, B, or C (equal numbers of males and females per group). Within groups, each participant received the novel food on four snack occasions. Group A received positive modelling of blue food consumption on the first and third occasions, but were alone when they received the foods on the second and fourth occasions; Group B had negative modelling on the first occasion, positive modelling on the third, and ate alone on the second and fourth; Group C ate alone on all four occasions. To measure generalisation, an additional blue food was presented in all second and fourth "alone" occasions. PARTICIPANTS: Thirty-five 5-7-year olds took part in Study 1, and 44 3-4-year olds in Study 2. RESULTS: All main predictions were confirmed except that positive peer modelling did not reverse the effects of negative modelling in the 3-4-year olds. CONCLUSION: Negative peer modelling inhibits novel food consumption, and its effects are particularly difficult to reverse in younger children.

What predicts post-traumatic stress following spinal cord injury?

OBJECTIVES: Spinal cord injury (SCI) is a severe, traumatic event and recently research into the role of post-traumatic stress disorder (PTSD) subsequent to the injury has become of increasing interest. This study has been conducted in order to investigate potential risk factors for the development of post-traumatic stress disorder symptoms in those with SCI. DESIGN: This cross-sectional study used multiple regression analysis to look for associations between post-traumatic stress symptom severity, SCI-related factors and previously identified risk factors for PTSD such as dysfunctional cognitions, demographic factors and personality predispositions (neuroticism, alexithymia). METHOD: A total of 102 participants with SCI completed measures of post-traumatic stress severity, acceptance of injury, post-traumatic cognitions, social support, neuroticism and alexithymia. In addition, information about type, level and cause of the SCI was assessed. RESULTS: High levels of post-traumatic stress symptoms were found. Potential risk factors for the development of PTSD were negative cognitions of self and neuroticism. Variables that added to the variance explained by the models included time since injury and difficulty identifying feelings. Acceptance of injury was mediated by negative cognitions of the self and neuroticism. CONCLUSIONS: The study highlights the need for services to be aware of the psychological difficulties experienced by this client group. An important finding is that the acceptance of the injury is mediated by negative cognitions of the self which need to be identified as potential risk factors in order to prevent the development of post-traumatic symptoms in this population.

Individual cognitive stimulation therapy for dementia: a clinical effectiveness and cost-effectiveness pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Group cognitive stimulation therapy programmes can benefit cognition and quality of life for people with dementia. Evidence for home-based, carer-led cognitive stimulation interventions is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of carer-delivered individual cognitive stimulation therapy (iCST) for people with dementia and their family carers, compared with treatment as usual (TAU). DESIGN: A multicentre, single-blind, randomised controlled trial assessing clinical effectiveness and cost-effectiveness. Assessments were at baseline, 13 weeks and 26 weeks (primary end point). SETTING: Participants were recruited through Memory Clinics and Community Mental Health Teams for older people. PARTICIPANTS: A total of 356 caregiving dyads were recruited and 273 completed the trial. INTERVENTION: iCST consisted of structured cognitive stimulation sessions for people with dementia, completed up to three times weekly over 25 weeks. Family carers were supported to deliver the sessions at home. MAIN OUTCOME MEASURES: Primary outcomes for the person with dementia were cognition and quality of life. Secondary outcomes included behavioural and psychological symptoms, activities of daily living, depressive symptoms and relationship quality. The primary outcome for the family carers was mental/physical health (Short Form questionnaire-12 items). Health-related quality of life (European Quality of Life-5 Dimensions), mood symptoms, resilience and relationship quality comprised the secondary outcomes. Costs were estimated from health and social care and societal perspectives. RESULTS: There were no differences in any of the primary outcomes for people with dementia between intervention and TAU [cognition: mean difference -0.55, 95% confidence interval (CI) -2.00 to 0.90; p-value = 0.45; self-reported quality of life: mean difference -0.02, 95% CI -1.22 to 0.82; p-value = 0.97 at the 6-month follow-up]. iCST did not improve mental/physical health for carers. People with dementia in the iCST group experienced better relationship quality with their carer, but there was no evidence that iCST improved their activities of daily living, depression or behavioural and psychological symptoms. iCST seemed to improve health-related quality of life for carers but did not benefit carers' resilience or their relationship quality with their relative. Carers conducting more sessions had fewer depressive symptoms. Qualitative data suggested that people with dementia and their carers experienced better communication owing to iCST. Adjusted mean costs were not significantly different between the groups. From the societal perspective, both health gains and cost savings were observed. CONCLUSIONS: iCST did not improve cognition or quality of life for people with dementia, or carers' physical and mental health. Costs of the intervention were offset by some reductions in social care and other services. Although there was some evidence of improvement in terms of the caregiving relationship and carers' health-related quality of life, iCST does not appear to deliver clinical benefits for cognition and quality of life for people with dementia. Most people received fewer than the recommended number of iCST sessions. Further research is needed to ascertain the clinical effectiveness of carer-led cognitive stimulation interventions for people with dementia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN65945963. FUNDING: This project was funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 19, No. 64. See the NIHR Journals Library website for further information.

The incidence of admissions for schizophrenia and related psychoses in two cohorts: 1875-1924 and 1994-2010.

Objective To investigate changes in incidence of admissions for schizophrenia and related non-affective psychoses in North Wales. Design Data from two epidemiologically complete cohorts of patients presenting for the first time to mental health services in North Wales between 1875-1924 and 1994-2010 are used in this study to map the incidence of hospital admissions for schizophrenia and non-affective psychoses. Setting The North Wales Asylum Denbigh (archived patient case notes) and the North West Wales District General Hospital psychiatric unit. Population 3168 patients admitted to the North Wales Asylum Denbigh between 1875 and 1924 and 355 patients admitted to the District General Hospital psychiatric unit between 1994 and 2010. Results There was an increasing admission incidence for schizophrenia between 1875 and 1900, a higher admission rate in the 1990s for men, followed by a drop in rates of admission for both genders since 2006. Admission incidences switch from parity between the sexes in the historical period to a doubling of the admission rates for men compared with women in the modern period. This admission pattern differs from the admission patterns for affective psychoses or organic disorders. Conclusion There have been changes in the incidence of admissions for schizophrenia in North Wales.

Mortality in schizophrenia and related psychoses: data from two cohorts, 1875-1924 and 1994-2010.

OBJECTIVE: To investigate death rates in schizophrenia and related psychoses. DESIGN: Data from two epidemiologically complete cohorts of patients presenting for the first time to mental health services in North Wales for whom there are at least 1, and up to 10-year follow-up data have been used to calculate survival rates and standardised death rates for schizophrenia and related psychoses. SETTING: The North Wales Asylum Denbigh (archived patient case notes) and the North West Wales District General Hospital psychiatric unit. POPULATION: Cohort 1: The North Wales Asylum Denbigh (archived patient case notes). Of 3168 patients admitted to the North Wales Asylum Denbigh 1875-1924, 1074 had a schizophrenic or related psychosis. Cohort 2: Patients admitted between 1994 and 2010 to the North West Wales District General Hospital psychiatric unit, of whom 355 had first admissions for schizophrenia or related psychoses. RESULTS: We found a 10-year survival probability of 75% in the historical cohort and a 90% survival probability in the contemporary cohort with a fourfold increase in standardised death rates in schizophrenia and related psychoses in both historical and contemporary periods. Suicide is the commonest cause of death in schizophrenia in the contemporary period (SMR 35), while tuberculosis was the commonest cause historically (SMR 9). In the contemporary data, deaths from cardiovascular causes arise in the elderly and deaths from suicide in the young. CONCLUSIONS: Contemporary death rates in schizophrenia and related psychoses are high but there are particular hazards and windows of risk that enable interventions. The data point to possible interventions in the incident year of treatment that could give patients with schizophrenia a normal life expectancy.

The role of vocal practice in constructing phonological working memory.

PURPOSE: In this study, the authors looked for effects of vocal practice on phonological working memory. METHOD: A longitudinal design was used, combining both naturalistic observations and a nonword repetition test. Fifteen 26-month-olds (12 of whom were followed from age 11 months) were administered a nonword test including real words, "standard" nonwords (identical for all children), and nonwords based on individual children's production inventory (in and out words). RESULTS: A strong relationship was found between (a) length of experience with consonant production and (b) nonword repetition and between (a) differential experience with specific consonants through production and (b) performance on the in versus out words. CONCLUSIONS: Performance depended on familiarity with words or their subunits and was strongest for real words, weaker for in words, and weakest for out words. The results demonstrate the important role of speech production in the construction of phonological working memory.

Parenting intervention in Sure Start services for children at risk of developing conduct disorder: pragmatic randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder. DESIGN: Pragmatic randomised controlled trial using a block design with allocation by area. SETTING: Eleven Sure Start areas in north and mid-Wales. PARTICIPANTS: 153 parents from socially disadvantaged areas, with children aged 36-59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory. Participants were randomised on a 2:1 basis, 104 to intervention and 49 to remaining on the wait listing (control). Twenty (13%) were lost to follow-up six months later, 18 from the intervention group. INTERVENTION: The Webster-Stratton Incredible Years basic parenting programme, a 12 week group based intervention. MAIN OUTCOME MEASURES: Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home. Parents' self reported parenting competence, stress, and depression. Standardised and well validated instruments were used throughout. RESULTS: At follow-up, most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group. The intention to treat analysis for the primary outcome measure, the Eyberg child behaviour inventory, showed a mean difference between groups of 4.4 points (95% confidence interval 2.0 to 6.9, P<0.001) on the problem scale with an effect size of 0.63, and a mean difference of 25.1 (14.9 to 35.2, P<0.001) on the intensity scale with an effect size of 0.89. CONCLUSION: This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff. It has influenced policy within Wales and provides lessons for England where, to date, Sure Start programmes have not been effective. TRIAL REGISTRATION: ISRCTN46984318.

Antidepressants and suicide: risk-benefit conundrums.

There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. To shed light on this issue, this paper reviews available randomized controlled trials (RCTs), meta-analyses of clinical trials and epidemiological studies that have been undertaken to investigate the issue further. The original clinical studies raising concerns about SSRIs and suicide induction produced evidence of a dose-dependent link on a challenge-dechallenge and rechallenge basis between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicated that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, revealed an excess of suicidal acts on active treatments compared with placebo, with an odds ratio of 2.4 (95; confidence interval 1.6-3.7). This excess of suicidal acts also appears in epidemiological studies. The data reviewed here make it difficult to sustain a null hypothesis that SSRIs do not cause problems in some individuals. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.