The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy.

Imaging studies have shown that serum concentrations of the selective serotonin reuptake inhibitor citalopram correlate with serotonin transporter (5-HTT) occupancy in vivo. In patients with major depressive disorders treated with citalopram, 80% 5-HTT occupancy was considered to be necessary for maximal therapeutic effects, which requires citalopram serum concentrations of at least 50 ng/mL. The aim of this study was to compare treatment outcome in patients with citalopram serum concentrations greater than and less than 50 ng/mL after 7 days of treatment. This study included inpatients with acute major depressive disorder according to International Classification of Disease, 10th Revision who were treated with citalopram. In weekly intervals, the severity of depression was assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17), and serum concentrations of citalopram were measured from baseline until week 5. Fifty-five patients were eligible for this analysis. After 7 days of treatment, 19 patients showed citalopram serum concentrations of 50 ng/mL or greater; 36 patients had lower concentrations. Patients at greater than the 50-ng/mL threshold had (i) lower mean HAMD-17 sum scores from day 7 to end point (P e 0.018 for each analysis); (ii) a more pronounced HAMD-17 decrease (P e 0.019 for each analysis), and (iii) 23 days' shorter duration of hospitalization (P = 0.033) than patients with levels of citalopram less than 50 ng/mL. As regards adverse effects, both patient groups were not significantly different. Despite therapeutic doses, a significant number of patients had serum concentrations less than 50 ng/mL, and these were associated with an unfavorable treatment outcome; therapeutic drug monitoring is recommended to optimize dosing citalopram in the early phase of treatment.

Other factors contributing to the variability in disposition kinetics could not be ruled out in this study, suggesting that mCPP is not a suitable model drug to test serotonin 2C receptor activity in vivo.

Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.

A 59-year-old female patient was hospitalized on account of a depressive episode in the course of a long-standing bipolar disorder. On a combination of lithium (400 mg/day) and paroxetine (30 mg/day) she developed symptoms of shivering, high-frequency tremor of the upper and lower limbs, skin flush in the face, agitation, and slight impairment of mental focusing, suggestive of a serotonin syndrome. At this stage serum lithium and paroxetine levels were 0.63 mmol/l, and 693 ng/ml, respectively; the latter was six times higher than the upper concentrations seen in patients on this dosage of the drug. Consequently, the dosage of paroxetine was reduced to 10 mg/day, and lithium was continued. This regimen resulted in a steady-state paroxetine serum level of 390 ng/ml. The patient became symptom-free and the depressive episode attenuated, thus enabling us to discharge the patient.