Bi-directional association between depression and HF: An electronic health records-based cohort study.

To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs). This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions. 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4-6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89-2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17-1.54) after adjusting for all 16 comorbid chronic conditions. These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses

Factors affecting outcome in schizophrenia and their relevance for psychopharmacological treatment

A major focus of current treatment research in schizophrenia is the determinants of long-term outcome, including functional outcome and general medical well being, rather than just specific domains of psychopathology such as positive and negative symptoms, mood symptoms, and cognitive impairment. This focus does not negate the importance of the latter issues but sees them as factors contributing to long-term outcome to variable extents. A long-term treatment focus facilitates a more clinically relevant assessment of benefits versus risks of available treatments. For instance, atypical antipsychotic drugs as a group have clear advantages for several important domains of efficacy that may influence long-term outcome, but are also more expensive over the long term. Use of some agents may also result in deleterious physical health consequences as well as large additional costs over the long term owing to metabolic adverse effects. The present paper focuses on several key issues in schizophrenia which are important determinants of long-term outcome in schizophrenia, or influence choice of antipsychotic drugs, or both, including: (i) duration of untreated psychosis; (ii) impact of relapse on long-term outcome; (iii) limited efficacy for specific domains of psychopathology of current treatments; (iv) mortality owing to suicide; and (v) mortality owing to other causes (e.g. cardiovascular disease

Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: A CO-MED report

10.1016/j.jad.2011.04.032Journal of Affective Disorders1333467-476JADI

Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes.

Background: Acylcarnitines have important functions in mitochondrial energetics and beta-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+).Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ (R) p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups.Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+.Conclusions: In depressed patients treated with SSRIs, beta-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics

Interchangeability of gabapentin generic formulations in the Netherlands: a comparative bioavailability study

Item does not contain fulltextTo investigate the so-called "drift" with generic-generic drug substitution, a single-dose, four-way crossover comparative bioavailability study was performed involving 24 healthy subjects and three generic and one branded formulation of a tablet containing 800 mg gabapentin as test medication. The results showed that the 90% confidence intervals (CIs) for the area under the drug concentration-time curve (AUC0-t) and for the peak drug concentration (Cmax) were within the acceptance range of 80-125% for all comparisons. The safety profiles of the different gabapentin formulations were comparable. To conclude, all three generic formulations of gabapentin were found to be bioequivalent with the branded formulation and with each other, indicating that the formulations are interchangeable. These results strongly indicate the absence of "drift" with gabapentin generic-generic substitution.Clinical Pharmacology & Therapeutics (2013); 94 4, 519-524. doi:10.1038/clpt.2013.108