BackgroundStudies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.ObjectivesTo compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments.Design and settingCohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018.Participants24 516 people diagnosed with depression, aged 18–99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine.Main outcome measuresHospitalisation or death due to deliberate self-harm. Age–sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates.ResultsStandardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose.ConclusionsThere was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm.Clinical implicationsAddressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.

BackgroundAdjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin’s place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication.ObjectiveTo produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology.MethodsA list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be ‘adopted or adapted’ from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008–2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.FindingsWe confirmed that no published guideline—of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs.ConclusionAll 11 recommendations and 7 supporting good practice developed here were formulated de novo.Clinical implicationsThese recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.

BackgroundCompared with traditional screening questionnaires, computerised adaptive tests for severity of depression (CAT-DI) and computerised adaptive diagnostic modules for depression (CAD-MDD) show improved precision in screening for major depressive disorder. CAT measures have been tailored to perinatal women but have not been studied in low-income women of colour despite high rates of perinatal depression (PND).ObjectiveThis study aimed to examine the concordance between CAT and traditional measures of depression in a sample of primarily low-income black and Latina women.MethodsIn total, 373 women (49% black; 29% Latina) completed the Patient Health Questionnaire-9 (PHQ-9), CAD-MDD and CAT-DI at 845 visits across pregnancy and postpartum. We examined the concordance between continuous CAT-DI and PHQ-9 scores and between binary measures of PND diagnosis on CAD-MDD and the PHQ-9 (cut-off score >10). We examined cases with a positive PND diagnosis on the CAD-MDD but not on the PHQ-9 (‘missed’ cases) to determine whether clinic notes were consistent with CAD-MDD results.FindingsCAT-DI and PHQ-9 scores were significantly associated (concordance correlation coefficient=0.67; 95% CI 0.58 to 0.74). CAD-MDD detected 5% more case of PND compared with PHQ-9 (p<0.001). The average per-visit rate of PND was 14.4% (14.5% in blacks, 14.9% in Latinas) on the CAD-MDD, and 9.5% (9.8% in blacks, 8.8% in Latinas) on the PHQ-9. Clinical notes were available on 60% of ‘missed’ cases and validated CAD-MDD PND diagnosis in 89% of cases.ConclusionsCAD-MDD detected 5% more cases of PND in women of colour compared with traditional tests, and the majority of these cases were verified by clinician notes.Clinical implicationsUse of CAT in routine clinic care may address health disparities in PND screening.

Commentary on : Bergman H, Walker DM, Nikolakopoulou A, et al . Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia. Health Technol Assess 2017;21:1-218. Tardive dyskinesia (TD) is a relatively frequent side effect of long-term use of antipsychotics and there is conflicting evidence if the incidence of TD is lower with second-generation antipsychotics (excluding clozapine), compared with first-generation antipsychotics. Until now there is no evidence-based algorithm to prevent or to treat TD. This systematic review1 evaluated any intervention for treating or preventing deterioration of symptoms of antipsychotic-induced TD in adult patients. Included were all relevant studies, regardless of language, about adults who had used antipsychotic drugs for ≥3 months and in whom the antipsychotic doses had been stable for at least 1 month. The authors included 112 randomised trials and eight prospective cohort studies. Seventy-nine separate interventions were the focus of the trials, whereas prospective cohort studies focused on comparing different strategies for antipsychotics. These were grouped into three broad categories: 1. Reducing antipsychotic dose. 2. Switching antipsychotic drug. (3) Adjunctive treatments in …

QuestionOppositional defiant and conduct disorders (ODD and CD) start early and persist, incurring high individual and collective costs. To inform policy and practice, we therefore asked: What is the best available research evidence on preventing and treating these disorders?Study selection and analysisWe sought randomised controlled trials (RCTs) evaluating interventions addressing the prevention or treatment of behaviour problems in individuals aged 18 years or younger. Our criteria were tailored to identify higher-quality RCTs that were also relevant to policy and practice. We searched the CINAHL, ERIC, MEDLINE, PsycINFO and Web of Science databases, updating our initial searches in May 2017. Thirty-seven RCTs met inclusion criteria—evaluating 15 prevention programmes, 8 psychosocial treatments and 5 medications. We then conducted narrative synthesis.FindingsFor prevention, 3 notable programmes reduced behavioural diagnoses: Classroom-Centered Intervention; Good Behavior Game; and Fast Track. Five other programmes reduced serious behaviour symptoms such as criminal activity. Prevention benefits were long term, up to 35 years. For psychosocial treatment, Incredible Years reduced behavioural diagnoses. Three other interventions reduced criminal activity. Psychosocial treatment benefits lasted from 1 to 8 years. While 4 medications reduced post-test symptoms, all caused important adverse events.ConclusionsConsiderable RCT evidence favours prevention.Clinical implicationsEffective prevention programmes should therefore be made widely available. Effective psychosocial treatments should also be provided for all children with ODD/CD. But medications should be a last resort given associated adverse events and given only short-term evidence of benefits. Policymakers and practitioners can help children and populations by acting on these findings.

Attention-deficit/hyperactivity disorder (ADHD) is characterised by a persistent and impairing pattern of inattention and/or hyperactivity/impulsivity and it is one of the most common neuropsychiatric conditions. Evidence about interventions of adults with ADHD is growing rapidly and clinicians need a reliable summary of all the best available information in order to better inform their daily practice. We searched MEDLINE, PubMed, PsycINFO and Cochrane databases until 31 May 2016 for systematic reviews about pharmacological and non-pharmacological treatments in adults with ADHD and carried out a meta-review to address clinically relevant questions. We identified a total of 40 papers. Psychostimulants—such as methylphenidate, dexamphetamine, mixed amphetamine salts and lisdexamfetamine—and non-psychostimulants—such as atomoxetine—were the most studied agents. Overall, pharmacological treatments were significantly more efficacious than placebo (standardised mean difference (SMD) 0.45, 95% CI 0.37 to 0.52), albeit less well accepted (OR 1.18, 95% CI 1.02 to 1.36) and tolerated (OR 2.29, 95% CI 1.97 to 2.66). The effects of pharmacological treatment for individuals with co-occurring ADHD and substance use disorder are still uncertain. The evidence for the efficacy and effectiveness of non-pharmacological treatments of ADHD in adults, as well as the combination of pharmacological and non-pharmacological strategies, is only preliminary. In conclusion, while available evidence addressed mainly the efficacy and tolerability of psychostimulants and non-psychostimulants for ADHD core symptoms in the short term, we still need further empirical support for the non-pharmacological and multimodal treatments. A comprehensive evidence-informed hierarchy of ADHD drugs based on their efficacy and tolerability is not yet available but it should be the next research priority in the field.

ABSTRACT FROM: Clement S, Schauman O, Graham T, et al . What is the impact of mental health-related stigma on help-seeking? A systematic review of quantitative and qualitative studies. Psychol Med 2015;45:11–27. Stigma towards individuals with mental illness has been shown to have an association with reduced help seeking attitudes, intentions and behaviours. However, findings on the effects of stigma are variable and depend on factors such as the type of stigma examined, the mental health problem of interest, the help-seeking outcome assessed, the population targeted and the research design. The systematic review by Clement et al aimed to assess the impact of mental illness stigma on help seeking for mental health problems. The authors searched Medline, EMBASE, Sociological Abstracts, PsycInfo and CINAHL up to 2011. Three type of studies were included: studies that examined the association between stigma and help seeking, studies that tested stigma as a barrier to help seeking, and studies that examined processes underlying the relationship …

Antidepressants are widely used in the treatment of bipolar depression despite relatively meagre evidence for their efficacy and significant concerns that their prescription can precipitate an acute affective switch into mania/hypomania and that long-term administration can lead to mood instability. Therefore, the use of antidepressants to treat bipolar depression is an important but contentious issue that two recent studies, which provide important new evidence, attempt to inform. One study suggests that long-term continuation of antidepressants in patients with rapid-cycling bipolar disorder leads to a threefold increase in mood episodes during the first year of follow-up—supporting the notion that antidepressants can cause more harm than good, and that they should be used sparingly. However, this is countered by findings from the other study, which suggests that continuation antidepressant monotherapy provides patients with bipolar II disorder reasonable prophylaxis, and that the risk of switching into mania/hypomania is actually quite low. In addition to contrary findings both studies are modest in sample sizes and have significant design limitations and hence the debate remains unresolved. This brief perspective presents both views in the context of evidence and provides some key insights into the complexity of this challenging but common clinical issue.

ABSTRACT FROM: Eley TC, McAdams TA, Rijsdijk FV, et al . The Intergenerational Transmission of Anxiety: A Children-of-Twins Study. Am J Psychiatry 2015;172:630–7. Anxiety disorders can run in families and both genetic and environmental influences have been implicated in this association. Although paediatric twin studies are able to ascertain the proportion of variance in child/adolescent phenotypes due to genetic and environmental influences, to date, they have not been able to specify the extent to which genes and the environment contribute to the transmission of anxiety between parents and their children, that is, whether similarities in the amount of anxiety experienced by parents and their offspring are accounted for by sharing genes, living together or both. For this, other genetically sensitive designs are needed. The children-of twins model is one such design and involves adult twin pairs and their offspring.1 The …

ABSTRACT FROM: Fazel S, Wolf A, Change Z, et al. Depression and violence: a Swedish population study. Lancet Psychiatry 2015;2:224–32. Major mental disorders, such as schizophrenia and personality disorder, have been associated with a higher risk of committing violent crime.1 However, the relationship between depression and violent crime is still unclear. Interestingly, some authors have recently presented evidence that this relationship occurs in the opposite direction: individuals with major depression present a higher risk of having homicidal death. For instance, in Sweden, a nationwide cohort found an increased risk of homicidal death in individuals with major depression than in general population (HR=2.61; 95% CI 1.58 to 4.33).2 To clarify this issue, Fazel et al performed two longitudinal studies. In the first study, outpatients with at least two episodes of major depression, according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), were identified from the National …