Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II).

Formation constants for the calcium(II), magnesium(II) and zinc(II) complexes of the orally effective iron chelator, pyridoxal isonicotinoyl hydrazone (PIH) and three analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone (PpMBH) and pyridoxal m-fluorobenzoyl hydrazone (PmFBH) have been determined by potentiometry at 25 degrees C and I = 0.1 M [KNO3]. The four ligands bind calcium(II) weakly and magnesium(II) only slightly more strongly, as a 1:1 complex which is formed at pH greater than 8. The chelation of zinc(II) for all the ligands studied was greater than that for calcium(II) and magnesium(II), with complexation generally becoming significant at about pH 5. Thus, chelation of zinc(II) but not calcium(II) or magnesium(II) at physiological pH, 7.4 may be expected. Calculated values of the concentration of uncomplexed metal ion indicate that the selectivity of these ligands towards Fe(III) is comparable to that of the clinically used chelator desferrioxamine.

Pyridoxal complexes as potential chelating agents for oral therapy in transfusional iron overload.

Iron chelation therapy for patients maintained on a regular transfusion regime is at present best carried out by means of daily infusions of desferrioxamine (Hussain et al 1977; Pippard et al 1978) but this is onerous for the patient and has social and economic disadvantages. Many recent attempts to provide more effective drugs for iron chelation have been summarized by Jacobs (1979) and increasing attention is now being paid to the possibility of oral iron chelation therapy. Hoy et al (1979) showed that when isonicotinic acid hydrazide (INH) and pyridoxal are mixed in equimolar amounts a hydrazone is formed which chelates iron, and oral administration of this compound to rats results in an eightfold increase in faecal iron excretion. It is effective on repeated administration (Cikrt et al 1980), the main route of iron excretion being through the bile. Long term studies in the rat have not been successful in reducing the iron load of test animals and this appears to be related both to their high dietary iron content and instability of the hydrazone. Its effective shelf life at room temperature is no longer than one month and this is a considerable disadvantage from a therapeutic point of view. Pyridoxal is known to form a Schiff base with many amino acids and its reactivity has led us to examine complexes of pyridoxal with a number of substances in an attempt to find an alternative iron chelator of greater stability than the INH complex and of comparable effectiveness on oral administration. The screening procedures used were the effects on Chang cell iron metabolism (White et al 1976) and on iron excretion in the rat (Hoy et al 1979).