Longitudinal assessment of an anti-stigma campaign related to common mental disorders in rural India.

BACKGROUND: Stigma related to mental health and lack of trained mental health professionals is a major cause for an increased treatment gap, particularly in rural India. The Systematic Medical Appraisal, Referral and Treatment (SMART) Mental Health project delivered a complex intervention involving task sharing, an anti-stigma campaign and use of technology-based, decision-support tools to empower primary care workers to identify and manage depression, anxiety, stress and suicide risk.AimsThe aim of this article is to report changes in stigma perceptions over three time points in the rural communities where the anti-stigma campaign was conducted. METHOD: A multimedia-based anti-stigma campaign was conducted over a 3-month period in the West Godavari district of Andhra Pradesh, India. Following that, the primary care-based mental health service was delivered for 1 year. The anti-stigma campaign was evaluated in two villages and data were captured at three time points over a 24-month period (N = 1417): before and after delivery of the campaign and after completion of the health services delivery intervention. Standardised tools captured data on knowledge, attitude and behaviour towards mental health as well as perceptions related to help seeking for mental illnesses. RESULTS: Most knowledge, attitude and behaviour scores improved over the three time points. Overall mean scores on stigma perceptions related to help seeking improved by -0.375 (minimum/maximum of -2.7/2.4, s.d. 0.519, P < 0.001) during this time. Loss to follow-up was 10%. CONCLUSIONS: The data highlight the positive effects of an anti-stigma campaign over a 2-year period.Declaration of interestNone.

Common mental disorders and risk factors in rural India: baseline data from the SMART mental health project.

BACKGROUND: About 10% Indians suffer from stress, depression or substance use disorders. Few receive care for these problems, especially in rural areas. AIMS: As part of a broader initiative to deliver technology-enabled mental health services for rural communities (adults ≥18 years), information was collected about the prevalence of depression, anxiety and suicide risk. METHOD: The study was conducted in 12 villages in the West Godavari district of Andhra Pradesh. Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Additionally, data were collected about sociodemographic factors and stressful events, among others. RESULTS: Anxiety, depression and suicidal ideation affected 10.8, 14.4 and 3.5% of participants, respectively (N = 22 377). These were more common among women, and among those who were aged 30-59 years, uneducated, or divorced/ separated/ widowed. Stress due to financial loss was significant. CONCLUSIONS: The study identified a significant number of people at risk of depression, anxiety and suicide, and needing care. DECLARATION OF INTEREST: None.

Drug Interaction Potential of Osilodrostat (LCI699) Based on Its Effect on the Pharmacokinetics of Probe Drugs of Cytochrome P450 Enzymes in Healthy Adults.

BACKGROUND AND OBJECTIVES: Osilodrostat (LCI699) is an adrenal steroidogenesis inhibitor currently in late-phase clinical development as a potential treatment for Cushing's disease. This study evaluated the inhibitory effect of osilodrostat on the pharmacokinetics of probe substrates of the cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, CYP2D6, and CYP3A4. METHODS: Healthy adult volunteers received single-dose cocktail probe substrates [caffeine (100 mg), omeprazole (20 mg), dextromethorphan (30 mg), and midazolam (2 mg)] followed by a 6-day washout. Subjects then received a single dose of osilodrostat 50 mg followed by a single dose of cocktail probe substrates. RESULTS: Nineteen of twenty subjects (ten were male) completed the study. Mean age, body weight, and body mass index were 41.8 years, 73.0 kg, and 24.4 kg/m2. Geometric mean ratio of the area under the concentration-time curve from time zero to the last measureable concentration and 90% confidence intervals of probe substrate exposure with osilodrostat were: caffeine (CYP1A2 probe substrate), 2.33 (2.10-2.59); omeprazole (CYP2C19), 1.91 (1.74-2.11); dextromethorphan (CYP2D6), 1.48 (1.34-1.63); and midazolam (CYP3A4/5), 1.50 (1.41-1.60). Corresponding values for geometric mean ratio of maximum plasma concentration (90% confidence interval) for the change in substrate exposure were 1.07 (0.988-1.15), 1.61 (1.40-1.84), 1.35 (1.21-1.50), and 1.47 (1.32-1.62). CONCLUSIONS: Osilodrostat is a moderate inhibitor of CYP1A2 and CYP2C19 and a weak inhibitor of CYP2D6 and the most clinically important CYP enzyme, CYP3A4. Osilodrostat is unlikely to significantly increase the exposures of other medications cleared by CYP3A4. These findings are clinically relevant given that Cushing's disease is a chronic condition often requiring multiple medications and that most other therapies have significant drug interaction potential.

Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF-1 suppression to octreotide LAR in healthy volunteers.

AIMS: The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation. METHODS: This was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg. RESULTS: One hundred and twenty-two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four- to five-fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml(-1) h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF-1. Maximum inhibition of IGF-1 at steady-state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related. CONCLUSIONS: Octreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.