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Publication Systematic Review and Meta-Analysis: The Association Between Newer-Generation Antidepressants and Insomnia in Children and Adolescents With Major Depressive Disorder(Elsevier, 2025-01) Türkmen, Cagdas; Machunze, Noah; Lee, Alycia M; Bougelet, Emilie; Ludin, Nicola M; de Cates, Angharad N; Vollstädt-Klein, Sabine; Bach, Patrick; Kiefer, Falk; Burdzovic Andreas, Jasmina; Kamphuis, Jeanine; Schoevers, Robert A; Emslie, Graham J; Hetrick, Sarah E; Viechtbauer, Wolfgang; van Dalfsen, Jens H; University of Heidelberg; University of Auckland; University of Oxford; Coventry and Warwickshire NHS Partnership Trust; German Center for Mental Health (DZPG); Norwegian Institute of Public Health; University of Oslo; University Medical Center Groningen; University of Texas Southwestern Medical Center, Dallas; Children's Medical Center, Dallas; Maastricht University; Psychiatry; Medical and Dental; de Cates, Angharad NObjective: To examine the association between newer generation antidepressants and insomnia as an adverse event (AE) in the treatment of children and adolescents with major depressive disorder (MDD). Method: A systematic search was performed in major databases (inception to August 31, 2023) to retrieve double-blind, placebo-controlled, randomized controlled trials (RCTs) evaluating the safety of 19 antidepressants in the acute treatment (initial 6-12 weeks) of children and adolescents ≤18 years of age with MDD (primary analyses). RCTs in anxiety disorders and obsessive-compulsive disorder (OCD) were retrieved from a recent meta-analysis and included in complementary analyses. A mixed-effects logistic regression model was used to compare the frequency of insomnia in the antidepressant relative to the placebo group. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Results: In total, 20 trials in MDD (N = 5,357) and 8 trials in anxiety disorders and OCD (N = 1,271) evaluating selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) were included. In MDD, antidepressant treatment was associated with a modest increase in the odds of insomnia compared with placebo (odds ratio [OR] = 1.65, 95% CI = 1.21-2.27, p = .002), with no significant difference between SSRIs and SNRIs. The RCTs showed low risk of bias or minor concerns for the assessment of insomnia. The odds of treatment-emergent insomnia were significantly lower in MDD (OR = 1.62; 95% CI = 1.21-2.15) compared to anxiety disorders and OCD (OR = 2.89; 95% CI = 1.83-4.57) for treatment with SSRIs (p = .03). Among individual antidepressants with evidence from ≥3 studies, sertraline had the highest OR (3.45; 95% CI = 1.91-6.24), whereas duloxetine had the lowest OR (1.38; 95% CI = 0.79-2.43). Conclusion: Children and adolescents are at a modestly increased risk for experiencing insomnia during the first 6 to 12 weeks of treatment with SSRIs and SNRIs. Antidepressant- and disorder-specific variability in the risk of treatment-emergent insomnia may be relevant to consider in clinical decision making. Study preregistration information: The association between newer generation antidepressants and insomnia in children and adolescents with major depressive disorder: a meta-analysis of randomized controlled trials; https://www.crd.york.ac.uk; CRD42023330506.Publication Insulin resistance and obesity, and their association with depression in relatively young people: findings from a large UK birth cohort(Cambridge University Press, 2019-03-11) Perry, Benjamin Ian; Khandaker, G. M.; Marwaha, Steven; Thompson, A.; Zammit, Stanley; Singh, Swaran P; Upthegrove, Rachel; University of Cambridge; Cambridgeshire and Peterborough National Health Service Foundation Trust; National Institute for Health Research Cambridge Biomedical Research Centre; University of Birmingham; Birmingham and Solihull Mental Health Foundation NHS Trust; Coventry and Warwickshire Partnership NHS Trust; University of Warwick; University of Bristol; Cardiff University; Birmingham Women's and Children's NHS Trust; Psychiatry; Medical and Dental; Thompson, A.; Singh, Swaran P.Background Depression frequently co-occurs with disorders of glucose and insulin homeostasis (DGIH) and obesity. Low-grade systemic inflammation and lifestyle factors in childhood may predispose to DGIH, obesity and depression. We aim to investigate the cross-sectional and longitudinal associations among DGIH, obesity and depression, and to examine the effect of demographics, lifestyle factors and antecedent low-grade inflammation on such associations in young people. Methods Using the Avon Longitudinal Study of Parents and Children birth cohort, we used regression analyses to examine: (1) cross-sectional and (2) longitudinal associations between measures of DGIH [insulin resistance (IR); impaired glucose tolerance] and body mass index (BMI) at ages 9 and 18 years, and depression (depressive symptoms and depressive episode) at age 18 years and (3) whether sociodemographics, lifestyle factors or inflammation [interleukin-6 (IL-6) at age 9 years] confounded any such associations. Results We included 3208 participants. At age 18 years, IR and BMI were positively associated with depression. These associations may be explained by sociodemographic and lifestyle factors. There were no longitudinal associations between DGIH/BMI and depression, and adjustment for IL-6 and C-reactive protein did not attenuate associations between IR/BMI and depression; however, the longitudinal analyses may have been underpowered. Conclusions Young people with depression show evidence of DGIH and raised BMI, which may be related to sociodemographic and lifestyle effects such as deprivation, smoking, ethnicity and gender. In future, studies with larger samples are required to confirm this. Preventative strategies for the poorer physical health outcomes associated with depression should focus on malleable lifestyle factors.Publication Perceptual abnormalities in an ultra-high risk for psychosis population relationship to trauma and co-morbid disorder(Wiley Online Library, 2017-08-09) O'Connor, Karen; Nelson, Barnaby; Cannon, Mary; Yung, Alison; Thompson, Andrew; University College Cork; University of Melbourne; Royal College of Surgeons, Dublin; University of Manchester; University of Warwick; Coventry and Warwickshire Partnership NHS Trust; Youth Psychiatry; Medical and Dental; Thompson, AndrewAims The aims of this study were 3-fold. We wished to investigate whether at baseline entry to an ultra-high risk (UHR) clinic whether: (1) perceptual abnormalities are more prevalent in those young people with co-morbid psychiatric diagnoses, (2) perceptual abnormalities are more prevalent in those young people with histories of childhood adversity (childhood trauma, bullying) and (3) perceptual abnormality type is associated with co-morbid psychiatric diagnoses or histories of childhood adversity. Methods In a sample of 118 UHR patients we investigated the relationship between perceptual abnormalities and non-psychotic diagnoses and adverse life events at entry to a UHR clinic. Results Depressive disorder at baseline was associated with increased odds of experiencing perceptual abnormalities (OR 3.59, P = .004), particularly visual perceptual abnormalities (OR 2.36, P = .02). Borderline personality disorder at baseline was associated with increased odds of any auditory perceptual abnormalities (OR 3.44, P = .04) and specifically second person perceptual abnormalities (OR 2.69, P = .04). A history of childhood trauma and childhood bullying were both associated with increased odds of experiencing perceptual abnormalities at baseline (trauma OR 6.30, P < .001; bullying OR 5.00, P = .01). Conclusions Our findings suggest that in the UHR population, certain types of perceptual abnormalities index risk for co-morbid non-psychotic disorder and indicate prior experience of childhood trauma. The use of detailed phenomenology of psychotic symptoms can help to shape our understanding of risk in UHR patients.Publication Pervasive refusal syndrome: systematic review of case reports(Springer Science+Business Media, 2021) Otasowie, John; Paraiso, Ann; Bates, Gordon; Surrey Memorial Hospital, 13750 96 Avenue, Surrey, British Columbia V3V 1Z2 Canada; Worcestershire Heath and Care Trust; Coventry and Warwickshire Partnership Trust; CAMHS; Additional Professional Scientific and Technical Field; Bates, GordonPervasive refusal syndrome (PRS) is a complex condition that affects young people leading to social withdrawal, inability or refusal to eat, drink, mobilise or speak. The affected individual regresses and is unable to self-care and quite characteristically will resist rehabilitation, worsen with praise or remain entirely passive. This systematic review was aimed at describing clinical features of PRS, current interventions and to summarise some of the nosological aspects of the condition. Without language restriction, an electronic search was conducted in Embase, PsychInfo, Medline, Cochrane library, and PubMed databases yielding 29 articles with a total of 79 cases. We performed a risk of assessment bias using an adapted Newcastle–Ottawa Scale and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 124 articles were identified, of which 29 were included and these yielded 79 cases. Seventy-six percent of the studies had a low rate of risk of assessment bias (good quality). Our results show that PRS overlaps with several conditions, mainly affects young females aged 7–15 years and has a recovery rate of 78% if diagnosed and treated early but the duration of inpatient treatment may last up to 9.44 months (8.82 SD). The patients had multiple inter-dependent risks. The major predisposing factors included vulnerable premorbid personality and pre-existing mental disorder. Precipitating factors were stressors such as infection and traumatic experiences. Enmeshed parent–child relationship served as a maintaining factor. The themes of treatment approach are essentially rehabilitative: (1) working collaboratively with patient and family, (2) having access to multidisciplinary team, and (3) peer/group supervision. This study has systematically evaluated a large sample of patients with PRS to ascertain its clinical features and the core elements of its treatment. Its key treatment approach is a multi-modal rehabilitative strategy that is compassionate, transparent and inclusive.