The therapeutic efficacy of lithium added to tricyclic antidepressants (TCA) or related thymoleptics was investigated in 27 endogenous depressive patients responding unsatisfactorily to these drugs alone. All patients received lithium during two weeks, however, with a delay of one week in 13 of them, the attribution to active treatment or placebo for the first seven days being double-blind. A statistically significant improvement compared to placebo occurred after lithium addition. The results of the double-blind part of the study as well as the observations during the total two-week period suggest that endogenous depression failing to respond to thymoleptic drug treatment can be improved within a short time by the co-administration of the two treatments in the indicated sequence. However, the proportion of patients improved and the rapidity of improvement noted in this study were less favorable than reported by the investigators who discovered the therapeutic principle.

A group of 119 patients suffering from a severe psychiatric postpartum disorder who were admitted for the first time in their life to a psychiatric hospital has been investigated. The onset of illness occurred within 3 months following delivery. The patients represented 92% of the total sample fulfilling the inclusion criteria. A follow-up investigation was performed after a mean of 21 years (range 2-35 years). Of the patients 66% had nonpuerperal psychotic episodes in later life. The diagnosis, taking into account the long-term course, was affective psychosis in 57%, schizoaffective psychosis in 18%, schizophreniform psychosis in 12%, brief reactive psychosis in 4% and schizophrenia in 9%. A bipolar psychosis was found in 31%. The relation of unipolar to bipolar psychoses corresponded to that in a control group of affectively ill women without puerperal onset. The frequency of a manic syndrome in bipolar psychoses at the index episode was the same as in nonpuerperal episodes, which does not suggest a mania-provoking pathoplastic effect of the puerperium. The comparison with female nonpuerperal controls matched for age and diagnosis revealed evidence of a better long-term course in the index patients. The risk of a puerperal relapse for further pregnancies was 35%. The global morbidity risk for functional psychoses in first-degree relatives was 11%, with affective psychoses representing the majority of secondary cases (6.8%). The index patients showed a nonsignificant lower morbidity risk in relatives than a control group of psychotically ill women without puerperal onset. The major aetiological factor found for postpartum psychoses is the relation of these disorders to functional psychoses. There is strong evidence that the postpartum period tends to provoke affective psychoses and other nonschizophrenic psychoses, but not, or only to a lesser degree, narrowly defined schizophrenias. The liability to puerperal decompensations suggests some common pathophysiological mechanism, the nature of which remains unknown.

Ten healthy volunteers were injected i.v. with 5 mg Ro 15-1788, a specific benzodiazepine antagonist, or placebo in a double-blind randomised design. In the EEG, Ro 15-1788 led--with some topographical variations--to a diminution of theta and alpha power, an increase of alpha mean frequency and a decrease of delta mean frequency. In auditory evoked potentials, the N1P2 and P2N2 amplitudes decreased. The electrophysiological changes induced by Ro 15-1788 are consistent with a central stimulant action. Ro 15-1788 induced some slight behavioural and subjective changes.

No abstract

Alpha 1-acid glycoprotein (AAG) is one of the plasma proteins that bind basic drugs, like amitriptyline (AT) and its metabolite nortriptyline (NT). Two types of genetic polymorphism have been described for AAG: polymorphic forms which, on electrophoresis of the native protein, give four patterns with 5, 6, 7 or 8 bands, and the variants which on by electrophoresis of the desialysed protein, give three patterns with 2 bands, FF, FS and SS. In 31 depressive patients, treated daily with 150 mg AT for 3 weeks, free and total plasma AT and NT were determined, as well as the AAG polymorphic forms and variants. There was only a weak negative correlation between the free fractions of AT and NT and total plasma AAG, but free AT and NT were strongly correlated with the S form (but not the F form) of AAG variants. The differences in binding might be the expression of a further genetic factor determining the steady-state plasma levels of tricyclic drugs.