A Constraint-Based Orbital-Optimized Excited State Method (COOX).

In this work, we present a novel method to directly calculate targeted electronic excited states within a self-consistent field calculation based on constrained density functional theory (cDFT). The constraint is constructed from the static occupied-occupied and virtual-virtual parts of the excited state difference density from (simplified) linear-response time-dependent density functional theory calculations (LR-TDDFT). Our new method shows a stable convergence behavior, provides an accurate excited state density adhering to the Aufbau principle, and can be solved within a restricted SCF for singlet excitations to avoid spin contamination.

Clozapine-induced obsessive-compulsive syndromes improve in combination with aripiprazole.

Patients with schizophrenia often experience comorbid obsessive-compulsive syndromes (OCSs). Within these patients, a significant subgroup developed secondary OCS during treatment with antiserotonergic, atypical antipsychotic agents such as clozapine. Although cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, in some cases, dose reductions of clozapine in combination approaches were able to alleviate OCS.

The oral, once-daily phosphodiesterase 4 inhibitor roflumilast lacks relevant pharmacokinetic interactions with inhaled budesonide.

This open-label, randomized, 3-period crossover study evaluated the pharmacokinetic interaction potential of roflumilast and budesonide following repeated coadministration to healthy male subjects (N = 12). Treatments consisted of oral roflumilast 500 mug, once daily, orally inhaled budesonide 800 mug, twice daily, and concomitant administration of both treatments for 7 days each. Roflumilast and roflumilast N-oxide in plasma and budesonide serum levels were measured by specific assays.