Three dose levels (5, 25, and 50 mg once daily) of the selective serotonin uptake inhibitor citalopram were compared in a four-week, double-blind trial in depressed patients. Serum levels of citalopram and desmethylcitalopram, and the inhibitory effect of serum on serotonin uptake by fresh platelets, were assessed once weekly during the trial. The serum concentrations of citalopram were highly correlated with inhibition of serotonin uptake. Less of the metabolite was found, it being detected only in the higher dose groups. Steady state levels of citalopram, attained after 1 week, were linearly related to dose. The relationship between improvement (percentage reduction in total score on the Montgomery-Asberg Depression Rating Scale) and serum level of citalopram indicated a lower limit of effect in endogenous depression at about 100 nM, corresponding to an average dose of 15 mg. Marked improvement was seen in ten patients with steady state levels in the range 70 to 335 nM. The ten nonendogenously depressed patients had steady state levels from 15 to 620 nM; complete remission was seen in the three with the lowest levels (15-25 nM). No significant correlation was found between serum drug level and the few reported side effects.

The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1--21/2 days). Steady state levels in the range 120--340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2--3 was recorded.

Serum concentrations of clopenthixol and flupenthixol have been determined during a four weeks dosage interval in patients trelated with intramuscular injections of clopenthixol decanoate or flupenthixol palmitate in Viscoleo®. Maximal drug levels were attained by the end of the first week after injection of either preparation. A period of exponential decline was then recorded. The half‐lives were estimated to 19 days for clopenthixol and 17 days for flupenthixol. These half‐lives most likely refer to the rate of release from the oil depot and not to elimination of drug. The mean ratio between maximal and minimal drug levels was 2.5 for clopenthixol and 3.7 for flupenthixol. Systemic clearance was estimated to about 0.7/min and 0.5/min, respectively.Significant correlation was found between the administered doses and recorded serum levels, between doses and estimated areas under the serum concentration curves, and also between areas and drug levels. The data indicate more limited individual variability than that seen with other psychotropic drugs, given orally.The study clearly demonstrates, that significant serum levels of active drug is maintained throughout the dosage interval by intramuscular injection of clopenthixol decanoate or flupenthixol palmitate in VisColed® every fourth week.

Correlations of serum nortriptyline (NT) and amitriptyline (AT) levels with psychomotor performance choice reaction performance, eye‐hand coordination, and divided attention was studied in two experiments each with 20 healthy subjects. In the first experiment serum NT level was measured with an isotope derivative method after treatment for 14 days with NT. In the second trial plasma AT and NT concentrations were measured with gas‐chromatography after treatment for 14 days with AT. No linear correlations between the levels of the antidepressants and performance variables were found. Low levels of NT (< 50 ng/ml) tended to shorten reaction time, and intermediate levels (50‐80 ng/ml) to prolong it, when compared with the reaction times during placebo. The correlation between serum NT levels and the increase of the tyramine dose in the tyramine pressor test was not significant. A new assay method for AT and NT is presented.