Ready, Willing and Able? An Investigation of the Theory of Planned Behaviour in Help-Seeking for a Community Sample with Current Untreated Depressive Symptoms

Applying health behaviour change models, such as the theory of planned behaviour (TPB), to help-seeking for mental health problems can address the deficit in health care utilisation. However, previous studies largely focused on help-seeking intentions and not behaviour, which might be problematic due to the intention-behaviour gap. Hence, TPB and help-seeking were examined in a German community sample with current untreated depressive symptoms: 188 adults (M-age = 50.34; SD = 16.19; 70.7% female) participated in a baseline interview and survey measuring components of the TPB (attitudes, subjective norms and perceived behavioural control) and help-seeking intentions. They reported actual help-seeking from mental health professionals via telephone surveys 3 and 6 months later. To better understand the potential gap between help-seeking intentions and behaviour and to investigate the contributions of readiness, willingness and ability to seek help, two path models were constructed in accordance with the TPB controlling for covariates. Attitudes (beta = .24), subjective norms (beta = .25) and self-efficacy (beta = .15) were significantly associated with intentions (R-2 = 26%), which predicted help-seeking (Cox and Snell's pseudo-R-2 = 23%); controllability did not predict help-seeking. In sum, the TPB provides a reliable framework to explore help-seeking behaviour for mental health problems. Based on these findings, prevention efforts should focus on readiness and willingness to seek help (e.g. foster positive attitudes and social support of treatment). However, the role of ability, operationalised as perceived behavioural control and (perceived) barriers to help-seeking, warrants further research, as self-efficacy but not controllability was associated with help-seeking

Metabolism of the Dual Orexin Receptor Antagonist ACT-541468, Based on Microtracer/Accelerator Mass Spectrometry

Background: As part of an integrated and innovative approach to accelerate the clinical development of the dual receptor antagonist ACT-541468, 6 healthy subjects in one cohort in a first-in-humans (FIH) study received an oral dose of 50 mg non-labeled ACT-541468 together with a microtracer amount of 250 nCi of C-14-labeled ACT-541468 to investigate its absorption, distribution, metabolism, and excretion (ADME).Methods: Using accelerator mass spectrometry (AMS), radiochromatograms were constructed for fractionated plasma, urine, and feces samples. Subsequently, the structures of the metabolites were elucidated using high performance liquid chromatography (HPLC) coupled with high resolution mass spectrometry.Results: In total 77 metabolites have been identified of which 30, 28, and 60 were present in plasma, urine, and feces, respectively. In plasma, the major metabolites were the mono-oxidized benzylic alcohol M3, the ACT-541468 aldehyde M1, formed by further oxidation of M3 in the benzylic position, and the doubly oxidized M10, formed by (1) benzylic oxidation of M3 (loss of one molecule of water and one molecule of ammonia) and (2) additional loss of water from the oxidized pyrrolidine ring of M5. Transformation of the pyrrolidine to a 6-membered ring was detected. Metabolites that accounted for more than 5% of total radioactivity in excreta were M2, which is also formed by oxidation at the benzylic position, M4, formed by demethylation of the methoxy-group, M7 and A6, both formed by oxidation of M4, and M10, the only major metabolite detected in urine.Conclusion: In conclusion, ACT-541468 is extensively metabolized predominantly by oxidative transformations.Stress-related psychiatric disorders across the life spa