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Background People with intellectual disabilities have very high rates of mental ill health. Standard psychosocial interventions designed for the general population may not be accessible for people with mild intellectual disabilities, and drug usage tends to be modified - 'start low and go slow'. This systematic review aims to synthesise the evidence on psychological, pharmacological and electroconvulsive therapy (ECT) interventions for adults with mild intellectual disabilities and mental ill health. Method PRISMA guidelines were followed. Medline, Embase, PsycINFO and CINAHL were searched, as was grey literature and reference lists of selected papers. Papers were selected based on pre-defined inclusion and exclusion criteria. A proportion of papers were double reviewed. Data was extracted using a structured table. Study registration: PROSPERO 2015:CRD42015015218. Results Initially, 18 949 records were identified. Sixteen studies were finally selected for inclusion; seven on psychological therapies, two on group exercise, five on antipsychotics and two on antidepressants. They do not provide definitive evidence for effectiveness of psychosocial interventions, nor address whether starting low and going slow is wise, or causes sub-optimum therapy. Conclusions There are few evidence-based interventions for people with mild intellectual disabilities and mental ill-health; existing literature is limited in quantity and quality. Group cognitive-behavioural therapies have some supporting evidence - however, further randomised control trials are required, with longer-term follow-up, and larger sample sizes. [ABSTRACT FROM AUTHOR]

Objective: The six items of the clinician-administrated Hamilton Depression Scale (HAM-D6) cover the core items of depressive states reflecting the antidepressive effect of medication. In this study, the two self-reported versions of the HAM-D6 have been psychometrically validated to ensure the unidimensionality of this administration form in patients with mild-to-moderate depression. Method: The item response theory analysis of Mokken was used to test the unidimensionality of both the Interactive Voice Recording System (IVRS) version of the HAM-D6 and a paper-and-pencil self-reported version (S-HAM-D6). Patients with typical major depression and with seasonal affective disorder were included. Results: The Mokken analysis showed that the two self-reported versions of the HAM-D6 obtained coefficients of homogeneity above 0.40, similar to the clinician-rated HAM-D6 and thus implying unidimensionality. By contrast, the full HAM-D17 versions (self-reported as well as clinician-rated) obtained coefficients of homogeneity below 0.40, implying that the HAM-D17 is a multidimensional scale. Conclusion: The analysis show that both the IVRS version and the S-HAM-D6 version are unidimensional self-rating scales for the measurement of depressive states. [ABSTRACT FROM AUTHOR]

Abstract: A paper considering the role of antidepressants for adults with major depression was recently published in the Lancet, a world leading medical journal (Cipriani et al. 2018). The review was the largest ever on this topic based on 28,552 citations including 522 trials comprising 116,477 participants. The authors note that, in adults with major depression, all antidepressants were more efficacious than placebo. In head‐to‐head studies, the authors also note that agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious. The authors report that the standardised mean difference was 0.3 a moderate effect size for any antidepressant over placebo, this is confirmatory of past reviews noting rather similar magnitudes of effect. In clinical terms the results suggest a choice for practitioners in regard to their individual patients. For many adult depressed patients however, there is also the implication that antidepressants may not work. The old adage ‘what works for whom’ remains unanswered. What does seem reasonable to conclude is that we have learnt that these medications are clinically effective and the questions for research now must be who is likely to benefit and who is not, how do these medicines work, and what is the best long‐term management of responders as the majority of studies have focused on acute response only. [ABSTRACT FROM AUTHOR]

Aim: Previous research indicates that preventive intervention is likely to benefit patients “at risk” of psychosis, in terms of functional improvement, symptom reduction and delay or prevention of onset of threshold psychotic disorder. The primary aim of the current study is to test outcomes of ultra high risk (UHR) patients, primarily functional outcome, in response to a sequential intervention strategy consisting of support and problem solving (SPS), cognitive‐behavioural case management and antidepressant medication. A secondary aim is to test biological and psychological variables that moderate and mediate response to this sequential treatment strategy. Methods: This is a sequential multiple assignment randomised trial (SMART) consisting of three steps: Step 1: SPS (1.5 months); Step 2: SPS vs Cognitive Behavioural Case Management (4.5 months); Step 3: Cognitive Behavioural Case Management + Antidepressant Medication vs Cognitive Behavioural Case Management + Placebo (6 months). The intervention is of 12 months duration in total and participants will be followed up at 18 months and 24 months post baseline. Conclusion: This paper reports on the rationale and protocol of the Staged Treatment in Early Psychosis (STEP) study. With a large sample of 500 UHR participants this study will investigate the most effective type and sequence of treatments for improving functioning and reducing the risk of developing psychotic disorder in this clinical population. [ABSTRACT FROM AUTHOR]

Objective We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials ( RCTs) compared to observational studies ( OSs). Method Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence. Results A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder. Conclusion Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]

Objective As part of a series of papers examining chronobiology ['Getting depression clinical guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013; 128(Suppl. 444):24-30; and 'Manipulating melatonin in managing mood' Boyce & Hopwood. ActaPsychiatrScand 2013; 128(Suppl. 444):16-23], in this article, we review and synthesise the extant literature pertaining to the chronobiology of depression and provide a preliminary model for understanding the neural systems involved. Method A selective literature search was conducted using search engines such as MEDLINE/ Pub Med, combining terms associated with chronobiology and mood disorders. Results We propose that understanding of sleep-wake function and mood can be enhanced by simultaneously considering the circadian system, the sleep homoeostat and the core stress system, all of which are likely to be simultaneously disrupted in major mood disorders. This integrative approach is likely to allow flexible modelling of a much broader range of mood disorder presentations and phenomenology. Conclusion A preliminary multifaceted model is presented, which will require further development and testing. Future depression research should aim to examine multiple systems concurrently in order to derive a more sophisticated understanding of the underlying neurobiology. [ABSTRACT FROM AUTHOR]

There is a high incidence of psychiatric comorbidity in people with epilepsy ( PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer ('second generation') antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term 'epileptogenesis': the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section. [ABSTRACT FROM AUTHOR]

Purpose. Child and family education regarding management of pediatric migraine is essential to reduce acute pain, prevent chronic daily migraine, and minimize the total number of headache attacks. This paper summarizes current evidence and provides a foundation for family teaching. Conclusions. Effective management of pediatric migraine can be achieved with a combination of individually tailored biobehavioral strategies, lifestyle modifications, and optimal scheduling of rescue and preventative pharmacologic treatment. Practice Implications. Included are goal setting recommendations, common triggers, key comorbidities, lifestyle modifications, principles of pharmacologic management, commonly used naturopathic compounds, and a link to an online downloadable teaching handout. [ABSTRACT FROM AUTHOR]

AIMS: This paper focuses on attitudes towards and use of self-chosen treatment among people prescribed antidepressants and discusses the implications for practitioners involved in medicines management. BACKGROUND: In the wide-ranging debate around the extension of non-medical prescribing in the UK the relationship between complementary and alternative therapies and prescribed medication has received little attention. Research indicates that self-treatment, including use of complementary and alternative therapies is burgeoning, yet there is uncertainty about the degree to which practitioners should be knowledgeable about therapies or be capable of advising clients on their use. Complementary and alternative therapy use is common among people with depression and greater knowledge of their use may be appropriate if health practitioners are to be able to support and inform people with depressive symptoms. METHODS: Qualitative methodology was adopted and 60 people from four primary care practices in the West Midlands, UK were interviewed individually and their self-reported treatment journeys documented. RESULTS: Almost two-thirds of participants had attempted to use self-chosen therapies during their recent illness though few had discussed their use with health service practitioners. Use of a range of self-chosen therapies was supported by a belief that they were natural, combined with a desire to avoid consulting health practitioners. Reasons for non-use of such therapies included confidence in health practitioners and caution about the possibility of drug interactions. CONCLUSIONS: Health practitioners require an awareness that people with mental health problems are using a range of self-chosen treatments and might consider the appropriateness of initiating discussions on self-chosen treatments with clients. This area requires greater debate and if necessary identification of an appropriate knowledge base. RELEVANCE TO CLINICAL PRACTICE: Assessment of common mental health problems should include discussion of patients' previous and current self-treatment. Such discussions will assist in identifying attitudes and beliefs towards health service treatment and provide a basis for selecting appropriate interventions. [ABSTRACT FROM AUTHOR]

This paper discusses methodological issues arising in the initial stages of a larger epidemiological case-control study. Practitioners from both Generic Mental Health and Substance Misuse Services (n = 170) were asked to identify which of their clients, from a time-limited caseload (n = 2341), had comorbid mental health and substance misuse problems. Although practitioners were provided with a definition of 'singly diagnosed' and 'dually diagnosed', it became apparent that these definitions were applied pragmatically, depending on the nature of the client's primary problem and the agency they were presenting to. Issues raised include the time period in which a client was considered to have a concurrent mental health problem and substance misuse, how a 'mental health problem' was defined and whether a personality disorder should be categorized as a 'mental health problem'. There was also some disagreement about whether clients who were being treated primarily by Substance Misuse Services, but were also taking prescribed antidepressants, implicitly had a 'mental health problem'. We raise these methodological issues, as they have implications for determining the prevalence of 'dual diagnosis' and the subsequent provision of services. [ABSTRACT FROM AUTHOR]

Post RM, Leverich GS, Nolen WA, Kupka RW, Altshuler LL, Frye MA, Suppes T, McElroy S, Keck, Jr. P, Grunze H, Walden J. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord 2003: 5: 396–406. © Blackwell Munksgaard, 2003 The risk-to-benefit ratio of the use of unimodal antidepressants (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and disagreement among experts in the field. This paper reviews new data on: (1) depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD discontinuation that are pertinent to the ongoing discussion and recommendations. In the first study reviewed, 258 outpatients with bipolar illness were assessed prospectively on a daily basis using the National Institute of Mental Health-Life Chart MethodTM (NIMH-LCM) for 1 year. In the second study, 127 bipolar depressed patients were randomized to 10 weeks of sertraline, bupropion, or venlafaxine, as adjuncts to mood stabilizers; non-responders were re-randomized and responders were offered a year of continuation treatment. In the final study, Altshuler et al. retrospectively and prospectively assessed the risk of depressive relapses in patients who remained on ADs after 2 months of euthymia compared with those who discontinued ADs. Despite intensive naturalistic treatment, the 258 outpatients with bipolar illness followed prospectively for 1 year showed three times as many days depressed as days manic, re-emphasizing the considerable depressive morbidity that remains in bipolar disorder despite the number of treatment options available. In the study of bipolar depressed patients randomized to one of three ADs, a range of severities and durations of hypomanic to manic switches were discerned following 175 trials of AD augmentation of treatment with a mood stabilizer. Of the acute 10-week trials, 9.1% were associated with switches into hypomania or mania and another 9.1% with a week or more of hypomania alone (with no to minimal dysfunction). In 73 continuation phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic and hypomanic switches, respectively. In the Altshuler et al. studies, those who remained well on any AD for more than 2 months (only 15–20% of those initially treated) and who continued on ADs showed a lesser rate of relapse into depression over 1 year (35 and 36% in the first and second study, respectively) compared with those who discontinued their ADs (68 and 70% relapsing into depression). Surprisingly, this continuation of ADs was associated with no increase in the rate of switching into mania compared with those stopping ADs. These data reveal that depression and depressive cycling remain a substantial problem in some two-thirds of intensively treated bipolar outpatients. Acute AD augmentation was associated with a modest response rate and 18.2% switched into a hypomanic to manic episode, and 35.6% of the continuation trials showed these two types of switches. Two separate studies suggest that in the very small subgroup who remain well on ADs for at least 2 months, one should consider continuation of this AD augmentation treatment, because AD discontinuation appears associated with a substantially increased risk of depression relapse over the subsequent year with no reduced risk of switching into mania. [ABSTRACT FROM AUTHOR]

Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology being used in psychiatric and neurological research in many centres around the world. rTMS has been accepted as a routine treatment of depression in Canada and Israel. To this point, it has been exclusively conducted by medical officers. As knowledge and experience grows, it is probable that professionals with other backgrounds will have the opportunity to play a role. The aim of this paper is to provide information that will be valuable to assistants. Electromagnetic principles are harnessed to deliver electric currents to localized regions of the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to be few. Much remains uncertain, however, even including the most appropriate treatment parameters. [ABSTRACT FROM AUTHOR]

Back in the March 2018 issue, I wrote a commentary titled "Why Don't SSRIs Work in the Medical Subspecialty Clinic?" The stimulus for this was our coverage that month of the results of the Chronic Kidney Disease Antidepressant Sertraline Trial, which found that sertraline was no better than placebo for depressive symptoms in patients with chronic kidney disease and major depression. I described the findings as "disappointing," and although I intended to convey that disappointment in the title of the commentary, perhaps I erred a bit on the nihilistic side. Happily, a paper we are covering this month allows me to offer a corrective. [ABSTRACT FROM AUTHOR]

The article examines the article "Antidepressants in Child and Adolescent Depression: Where are the bugs?," by Moreno and colleagues. The paper indicates the increasing use of antidepressant drugs in children and adolescents. The authors also analyzed the relative risk of suicide according to antidepressants corrected for psychiatric hospital contact to minimize the problem of confounding by indication.

Objective: This paper discusses strategies for achieving remission in major depressive disorder, summarizing the results of comparative studies of various antidepressants. Method: Antidepressant efficacy was determined as either response or remission, measured using the Hamilton Depression Rating Scale, the Clinical Global Impressions scale and other widely used instruments. Results: Study results suggest an advantage to pharmacotherapy that interacts with more than one neurotransmitter system, either as single mixed-activity drugs (e.g. clomipramine, mirtazapine and venlafaxine extended-release) or combinations of medications that are individually specific for a single neurotransmitter system. Conclusion: Remission should be the goal of antidepressant therapy. Treatment strategies include increasing the dosage of the chosen antidepressant; switching to an antidepressant with a different mechanism of action; augmenting one antidepressant with another agent; or using combination therapy. A substantial body of data indicates that for a subset of depressed patients, activation of multiple neurotransmitter systems is beneficial in achieving remission. [ABSTRACT FROM AUTHOR]

Objective: To review adverse outcomes following response in treatment of depression. Method: Review of published literature with particular emphasis on key papers. Results: Moderately high rates of relapse and recurrence are found in naturalistic follow-up studies of depressed patients receiving modern treatment. These are reduced but not abolished in controlled trials by continuation and maintenance treatment with antidepressants. Suicide rates in follow-up studies are much elevated compared with the general population. Social function is impaired and remits more slowly than depressive symptoms. A key outcome is the occurrence of incomplete remission with residual symptoms, which is associated with high relapse rates and impaired social function. Conclusion: It is important to achieve complete remission in depression. Elimination of residual symptoms is an important target for full treatment of the depressive episode, in order to avoid later adverse outcomes. [ABSTRACT FROM AUTHOR]