Plasma ratio tryptophan/neutral amino acids in relation to clinical response to paroxetine and clomipramine in patients with major depression.

The pretreatment plasma ratio of tryptophan (Trp) to other large neutral amino acids (LNAA), thought to reflect brain serotonin formation, was determined in 44 inpatients with major depression, who were subsequently treated double-blind on a fixed-dose schedule for 4 weeks with the selective serotonin uptake inhibitor paroxetine (n = 27) or clomipramine (n = 17). The study took place at four clinical centers. Endogenous and non-endogenous depressives were comparable with respect to the ratio Trp/LNAA and clinical improvement and were therefore analyzed together. The clomipramine group showed a significant inverse correlation between ratio Trp/LNAA and improvement, and patients with a ratio Trp/LNAA below the mean showed a trend towards greater improvement than patients with a higher ratio but with comparable serum drug levels. The improvement in the paroxetine group was significantly inversely correlated with the Trp concentration but not with the ratio Trp/LNAA. The findings accord with previous trials of various antidepressant treatments, in which about 25% of the variance in therapeutic response associates with pretreatment plasma amino acid profiles.

The Melancholia Scale and the Newcastle Scales. Item-combinations and inter-observer reliability.

The reliability of the total scores on three rating scales (Melancholia Scale and the two Newcastle Scales) and the algorithms leading to the Feighner, Research Diagnostic Criteria, and the DSM-III subtypes of depression have been compared. The degree of inter-observer agreements for the various item-combinations was significantly higher than would be expected by chance. The average agreement for each assessment system ranged from 80 to 93 per cent. This 7 to 20 per cent lack of total agreement probably reflects the limitation of clinical assessments including the influence of halo effects.

The Hamilton Anxiety Scale. Evaluation of homogeneity and inter-observer reliability in patients with depressive disorders.

In the present study the Hamilton Anxiety Scale (HAS), originally constructed for patients with neurotic anxiety, has been applied to patients with diagnosis of depressive disorders. The inter-rater reliability and homogeneity are evaluated and total scale score has been correlated to the Bech-Rafaelsen Melancholia Scale (BRMES). Twenty-two patients entered the study, 13 with endogenous depressions, and 9 with non-endogenous depressions when classified according to the ICD-8. For both scales the inter-rater reliability was found statistically significant. Concerning the homogeneity of the HAS, statistical significance was obtained for 7 items reflecting psychic anxiety, whereas in the BRMES statistical significance was found in all items apart from 2. Total scale score on HAS correlated positively with total score on BRMES for all 2 patients. However, when the patients were classified according to the ICD-8 this correlation seemed to be due to the endogenously depressed group as no significant correlation was seen for the group of non-endogenous depression. On the other hand, when the patients were classified according to the MULTI-CLAD system no significant intercorrelation of the HAS and BRMES scores was found within the subtypes of depression.

Arterial and venous concentrations of phenobarbital, phenytoin, clonazepam, and diazepam after rapid intravenous injections.

Arterial and venous concentrations of phenobarbital, phenytoin, clonazepam, and diazepam were followed for 12 hr after a rapid intravenous injection. Initial blood samples were collected at intervals of only 5 sec. The arterial curves were initially much higher and steeper than the venous. For all four drugs the arterial curves could be described as triexponential functions. The initial part of the arterial curves were used in determining the initial supply to and uptake rate in the organs.