Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients.

BACKGROUND: Dysthymic disorder is a relatively common illness that is often treated with antidepressants. Compared with the study of major depression, there has been little systematic study of potentiation strategies for antidepressant-refractory dysthymic disorder. METHOD: Following a patient's report of dramatic response to the addition of chromium supplementation to sertraline pharmacotherapy for dysthymic disorder (DSM-IV), the authors initiated a series of single-blind and open-label trials of chromium picolinate or chromium polynicotinate in the treatment of antidepressant-refractory dysthymic disorder. RESULTS: In a series of 5 patients, chromium supplementation led to remission of dysthymic symptoms. Single-blind substitution of other dietary supplements in each of the patients demonstrated specificity of response to chromium supplementation. CONCLUSION: Preliminary observations suggest that chromium may potentiate antidepressant pharmacotherapy for dysthymic disorder. Controlled studies are indicated to test the validity of these initial observations.

Resistance of leaf and stem fractions of tropical forage to chewing and passage in cattle.

The voluntary intake (VI) of separated leaf and stem fractions of a grass and legume (Panicum maximum and Lablab purpureus respectively) was determined using Hereford steers fistulated at the rumen and oesophagus. VI of leaf fractions was higher than that of the stem fraction (8.23 v. 3.67 kg/d, P less than 0.001) while that for the legume diets was higher than for the grass diets (6.65 v. 5.22 kg/d, P less than 0.05). The total number of eating chews per day was higher on the leaf than stem fraction (1.6 x 10(4) v. 9.8 x 10(3), P less than 0.05). The mean number of rumination chews (2.4 x 10(4)) was similar (P greater than 0.05) for all four diets. The mean resistance of large particles (LP, i.e. retained on a 1.18 mm sieve during wet sieving) to breakdown (chews per g LP breakdown) during eating was lower for leaf than stem fractions (8.4 v. 23.7) and lower for the grass than legume diets (10.5 v. 21.6). The mean resistance to breakdown of LP by rumination (chews per g LP breakdown) was lower in leaf than in stem fractions (8.2 v. 13.2, P less than 0.01) and higher in grass than in legume (12.5 v. 9.0, P less than 0.05). The resistance of LP to breakdown during rumination was higher than during eating for the grass diets, but was lower for the legume. Fractional passage rates (FPR) of small particles (i.e. passing through a 1.18 mm sieve during wet sieving) from the reticulo-rumen were negatively related to dimensions of particles, with greater ease of outflow for legume than for grass particles of the same length or diameter. When corrected for content of cellulase-indigestible fibre, FPR of small particles of leaf was greater than for small stem particles. It was concluded that VI of tropical forages was associated with the resistance of LP to breakdown by chewing during both eating and rumination and that the patterns of escape of small particles from the reticulo-rumen were only partially explicable in terms of particle dimensions, and that other properties of the particles may be of importance.

Breakdown of large particles in forage by simulated digestion and detrition.

To determine the importance of digestion and detrition (rubbing) in the rumen on the breakdown of large particles (LP) in the leaf and stem fractions of temperate and tropical forages, a study was made using a digestion-detrition simulator. Large-particle breakdown was measured in forage samples subjected to 48-h digestion or 48-h digestion plus detrition. Digestion caused a breakdown of 14% +/- 1.9% (means +/- SE) of the LP, and a further 8 +/- 1.9% were broken down by detrition. There was no difference in breakdown between temperate and tropical forages. The mean breakdown in vitro of LP of temperate forage was similar to that reported in vivo (21 vs 17%), but the breakdown of leaf fraction in vitro was twice that observed in vivo, possibly due to the greater breakdown in vivo of the LP during primary mastication. Both digestion and detrition cause a reduction in size of forage particles in vitro; this result supports conclusions drawn from in vivo studies.

Large particle breakdown by cattle eating ryegrass and alfalfa.

The proportion of large particles (LP) broken down to small, insoluble particles by primary mastication (eating), rumination, digestion and detrition (rubbing) was determined for separated leaf and stem fractions of perennial ryegrass (Lolium perenne) and alfalfa (Medicago sativa) fed to cattle cannulated at the esophagus. Large particles were defined as those particles retained during wet sieving on a screen with an aperture of 1.18 mm. Reduction in weight of particles caused by solubilizing or digestion was not considered to be particle breakdown per se, and particles were corrected for this loss in weight. The proportion of LP in the forage broken down by primary mastication was 25 +/- 1.9% (means +/- SE). Breakdown of LP by rumination was calculated from the weight of total particles regurgitated and the proportion of LP in the regurgitated and swallowed remasticated material. The weight of LP regurgitated was corrected for the dry matter lost by digestion using lignin ratio in the LP entering the rumen and of the regurgitated digesta. Rumination accounted for 50 +/- 1.5% of LP breakdown. Fecal loss accounted for 8 +/- .8% of the LP in forage. Breakdown of LP by digestion and detrition was calculated as 17 +/- 1.3% from the difference between the LP eaten and those broken down by primary mastication, rumination and passing out in the feces. The significance of these results for predicting voluntary intake from laboratory analysis is considered.

A comparison of phenelzine and imipramine in depressed inpatients.

Phenelzine and imipramine were compared double-blind, in 43 depressed inpatients. A placebo week preceded drug treatment; this allowed early identification of placebo responders who did not therefore enter the study. After three weeks treatment, the two drugs were equally effective on Hamilton, Beck and SCL-90 measures of depression and anxiety. On the the SCL-90 scales of hostility and paranoia imipramine was more effective; in some patients phenelzine was associated with increased hostility. Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - (mean 81 mg/day phenelzine and 144 mg/day imipramine).

Platelet monoamine oxidase activity and the classification of depression.

An attempt was made to compare platelet monoamine oxidase (MAO) activity in descriptively based types of nonbipolar depression. Platelet MAO activity was significantly higher in depression secondary to chronic anxiety, compared with primary unipolar depression and depression secondary to borderline personality, and in women compared with men. No significant differences were observed between endogenous-nonendogenous, delusional-nondelusional, psychomotor states, or different age groups.

Catechol-O-methyltransferase activity and classification of depression.

Red blood cell catechol-O-methyltransferase (COMT) activity was compared across different depressive diagnoses. In a sample of 88 depressed inpatients, using defined criteria, no difference was found in respect of enzyme activity and the following categories: primary, secondary, delusional, nondelusional, endogenous, nonendogenous (neurotic), characterological depressions. COMT did not vary with age or sex. A significant increase in COMT activity was noted in agitated, depressed males, as compared to other groups.

Acetylation phenotype, platelet monoamine oxidase inhibition, and the effectiveness of phenelzine in depression.

The authors treated 16 depressed patients with up to 90 mg/day of phenelzine. After acetylation phenotype was determined and platelet monoamine oxidase (MAO) activity measured, no significant relationship was observed between clinical improvement and acetylation phenotype or between MAO inhibition and acetylation. Discrepant findings regarding acetylation phenotype and the effects of phenelzine are discussed. The authors do not recommend a sulfamethazine phenotype test as a predictor of outcome for phenelzine.

Inhibition of platelet monoamine oxidase in depressed subjects treated with phenelzine.

The authors treated 19 depressive inpatients double-blind with a mean dose of 78 mg/day of phenelzine for 3 weeks to determine the possible relationship between monoamine oxidase (MAO) inhibition and the effectiveness of phenelzine. Clinical ratings made on the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the SCL-90 indicated a minimum of 60% MAO inhibition had to be achieved for the drug to be consistently beneficial.

Antidepressant drug therapy in psychotic depression.

Imipramine and phenelzine were ineffective in the treatment of five primary unipolar depressives with delusions, even when plasma levels of imipramine and desmethylimipramine or activity of platelet monoamine oxidase suggested that an adequate dose of drug had been given. Four patients went on to receive ECT and all responded well. Five non-delusional patients responded satisfactorily to the antidepressant drug given. Nine out of ten subjects were women. Non-delusional patients showed some placebo response. ECT is considered to be the treatment of choice in the acute phase of delusional depression in women.

Platelet monoamine oxidase activity in schizophrenia.

The activity of platelet monoamine oxidase in 12 chronic schizophrenic patients was not significantly different from that in a matched group of normal individuals. The authors emphasize the importance of simultaneous processing of control and patient blood samples and the use of carefully controlled techniques, since relatively minor changes in procedure can markedly influence platelet yield and leucocyte contamination.

Red blood cell catechol O-methyl transferase and response to imipramine in unipolar depressive women.

When baseline red blood cell catechol O-methyltransferase (COMT) was measured in 15 unipolar depressive women, the authors found a linear correlation between COMT and response to imipramine (best outcome occurring at low COMT). The results of this study were not related to such variables as intensity of depression, family history, or psychiatric history. The authors suggest that this assay may be useful either as a predictor of response to the drug or as a guide in choosing the optimum dose.

Catechol O-methyltransferase in red blood cells of schizophrenic, depressed, and normal human subjects.

Catechol O-methyltransferase of lysed human red blood cells was assayed under optimal conditions, using saturating concentrations of the substrates, S-adenosyl-L-methionine and 3-4-dihydroxybenzoic acid. The mean enzyme activity found in 24 normal subjects was 29-2 nmol/hr/ml RBC. The mean activity in blood of 33 female unipolar depressives was not significantly different from normal. However, higher enzyme activities were observed in the blood of 11 schizophrenic patients (38-9 nmol/hr/ml RBC). Partially purified enzyme preparations from blood of normal and schizophrenic individuals were indistinguishable with respect to substrate specificities, isoelectric pH values, and ratios of the two O-methylated products. Therefore it is unlikely that any defect in O-methylation which may occur in schizophrenia can be attributed to a change in the intrinsic properties of erythrocyte catechol O-methyltransferase.