A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Dimensional analysis of depressive, anxious and somatic symptoms presented by primary care patients and their relationship with ICD-11 PHC proposed diagnoses.

BACKGROUND: A study conducted as part of the development of the Eleventh International Classification of Mental Disorders for Primary Health Care (ICD-11 PHC) provided an opportunity to test the relationships among depressive, anxious and somatic symptoms in PHC. METHOD: Primary care physicians participating in the ICD-11 PHC field studies in five countries selected patients who presented with somatic symptoms not explained by known physical pathology by applying a 29-item screening on somatic complaints that were under study for bodily stress disorder. Patients were interviewed using the Clinical Interview Schedule-Revised and assessed using two five-item scales that measure depressive and anxious symptoms. Structural models of anxious-depressive symptoms and somatic complaints were tested using a bi-factor approach. RESULTS: A total of 797 patients completed the study procedures. Two bi-factor models fit the data well: Model 1 had all symptoms loaded on a general factor, along with one of three specific depression, anxiety and somatic factors [x2 (627) = 741.016, p < 0.0011, RMSEA = 0.015, CFI = 0.911, TLI = 0.9]. Model 2 had a general factor and two specific anxious depression and somatic factors [x2 (627) = 663.065, p = 0.1543, RMSEA = 0.008, CFI = 0.954, TLI = 0.948]. CONCLUSIONS: These data along with those of previous studies suggest that depressive, anxious and somatic symptoms are largely different presentations of a common latent phenomenon. This study provides support for the ICD-11 PHC conceptualization of mood disturbance, especially anxious depression, as central among patients who present multiple somatic symptoms.

Primary care physicians' use of the proposed classification of common mental disorders for ICD-11.

Background: The World Health Organization is revising the classification of common mental disorders in primary care for ICD-11. Major changes from the ICD-10 primary care version have been proposed for: (i) mood and anxiety disorders; and (ii) presentations of multiple somatic symptoms (bodily stress syndrome). This three-part field study explored the implementation of the revised classification by primary care physicians (PCPs) in five countries. Methods: Participating PCPs in Brazil, China, Mexico, Pakistan and Spain were asked to use the revised classification, first in patients that they suspected might be psychologically distressed (Part 1), and second in patients with multiple somatic symptoms causing distress or disability not wholly attributable to a known physical pathology, or with high levels of health anxiety (Part 2). Patients referred to Part 1 or Part 2 underwent a structured diagnostic interview. Part 3 consisted of feedback from PCPs regarding the classification. Results: In Part 1, anxious depression was the most common disorder among referred patients. PCPs assigned the highest severity ratings to anxious depression, and the next highest to current depression; current anxiety was rated as least severe. Considerable overlap was found between bodily stress syndrome (BSS) and health anxiety (HA). The psychiatric interview recorded higher rates of mood and anxiety disorders diagnoses among patients with BSS than did PCPs. PCPs' satisfaction with the revised classification was high. Conclusions: Results generally supported the inclusion of the new categories of anxious depression, BSS and HA for ICD-11 PHC and suggested that PCPs could implement these categories satisfactorily.

Exploring Lived Experiences of Adolescents Presenting with Self-Harm and Their Views about Suicide Prevention Strategies: A Qualitative Approach.

Suicide is a serious global public health problem and the third leading cause of death in those 15-35 years old. Self-harm is the major predictor of future suicide attempts and completed suicide yet remains poorly understood. There is limited evidence on effective interventions for adolescents who present with self-harm. To identify and develop acceptable preventive and therapeutic interventions it is essential to understand the factors that contribute to self-harm and suicide in young people, in the context of their emotions, interpersonal difficulties, available support and prevention strategies. This qualitative study aimed at exploring the lived experiences of adolescents presenting with self-harm and their views about potential prevention strategies. Semi-structured interviews with 16 adolescents (12-18 years) presenting with a self-harm episode in a public hospital in Pakistan. A topic guide was developed to facilitate the interviews. The following themes emerged using the framework analysis; predisposing factors (interpersonal conflicts, emotional crisis etc.), regret and realization that self-harm is not the only option, perceived impact of self-harm, and suggestions for suicide prevention strategies (sharing, distraction techniques, involvement of family). This study may help in refining a contextual and culturally based explanatory model of self-harm in adolescents and in informing development of culturally acceptable interventions.

Diagnostic consequences of a new category of anxious depression and a reduced duration requirement for anxiety symptoms in the ICD-11 PHC.

BACKGROUND: A new diagnosis of anxious depression (AD), characterized by both depressive and anxious symptoms at case level, has been proposed for the classification of mental disorders for primary care for ICD-11 (ICD-11 PHC). The ICD-11 PHC proposes a duration requirement for anxiety symptoms of 2 weeks, in line with the requirement for depressive symptoms. This study examined diagnostic assignment under ICD-11 PHC as compared to the previous classification, the ICD-10 PHC, and the relationship of anxiety duration to disability and suicidal ideation. METHODS: Primary care physicians in five countries referred patients based on either perceived psychological distress or distressing somatic symptoms to a research assistant who administered a computer-guided diagnostic interview. Complete data were obtained for 2279 participants. RESULTS: Under ICD-11 PHC 47.7% participants received a diagnosis of AD and had greater disability than other diagnostic groups. Under ICD-10 PHC, in addition to meeting requirements for depressive episode, most of these patients met requirements for either generalized anxiety disorder (41.5%) or mixed anxiety and depressive disorder (45.4%). One third of individuals diagnosed with AD had anxiety durations between 2 weeks and 3 months and presented as much disability and suicidal ideation as individuals with longer anxiety durations. LIMITATIONS: The study was not designed to establish prevalence of these conditions. CONCLUSION: The proposed ICD-11 PHC encourages early identification and management of significant anxiety symptoms in primary care, particularly when these co-occur with depression. This study provides support for the clinical relevance of these symptoms and the importance of early identification.

Screening for anxiety, depression, and anxious depression in primary care: A field study for ICD-11 PHC.

BACKGROUND: In this field study of WHO's revised classification of mental disorders for primary care settings, the ICD-11 PHC, we tested the usefulness of two five-item screening scales for anxiety and depression to be administered in primary care settings. METHODS: The study was conducted in primary care settings in four large middle-income countries. Primary care physicians (PCPs) referred individuals who they suspected might be psychologically distressed to the study. Screening scales as well as a structured diagnostic interview, the revised Clinical Interview Schedule (CIS-R), adapted for proposed decision rules in ICD-11 PHC, were administered to 1488 participants. RESULTS: A score of 3 or more on one or both screening scale predicted 89.6% of above-threshold mood or anxiety disorder diagnoses on the CIS-R. Anxious depression was the most common CIS-R diagnosis among referred patients. However, there was an exact diagnostic match between the screening scales and the CIS-R in only 62.9% of those with high scores. LIMITATIONS: This study was confined to those in whom the PCP suspected psychological distress, so does not provide information about the prevalence of mental disorders in primary care settings. CONCLUSIONS: The two five-item screening scales for anxiety and depression provide a practical way for PCPs to evaluate the likelihood of mood and anxiety disorders without paper and pencil measures that are not feasible in many settings. These scales may provide substantially improved case detection as compared to current primary care practice and a realistic alternative to complex diagnostic algorithms used by specialist mental health professionals.

A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol.

BACKGROUND: The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries. METHODS/DESIGN: A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis. DISCUSSION: The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015.

Multiple somatic symptoms in primary care: A field study for ICD-11 PHC, WHO's revised classification of mental disorders in primary care settings.

OBJECTIVE: A World Health Organization (WHO) field study conducted in five countries assessed proposals for Bodily Stress Syndrome (BSS) and Health Anxiety (HA) for the Primary Health Care Version of ICD-11. BSS requires multiple somatic symptoms not caused by known physical pathology and associated with distress or dysfunction. HA involves persistent, intrusive fears of having an illness or intense preoccupation with and misinterpretation of bodily sensations. This study examined how the proposed descriptions for BSS and HA corresponded to what was observed by working primary care physicians (PCPs) in participating countries, and the relationship of BSS and HA to depressive and anxiety disorders and to disability. METHOD: PCPs referred patients judged to have BSS or HA, who were then interviewed using a standardized psychiatric interview and a standardized measure of disability. RESULTS: Of 587 patients with BSS or HA, 70.4% were identified as having both conditions. Participants had an average of 10.9 somatic symptoms. Patients who presented somatic symptoms across multiple body systems were more disabled than patients with symptoms in a single system. Most referred patients (78.9%) had co-occurring diagnoses of depression, anxiety, or both. Anxious depression was the most common co-occurring psychological disorder, associated with the greatest disability. CONCLUSION: Study results indicate the importance of assessing for mood and anxiety disorders among patients who present multiple somatic symptoms without identifiable physical pathology. Although highly co-occurring with each other and with mood and anxiety disorders, BSS and HA represent distinct constructs that correspond to important presentations in primary care.