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Serum concentrations of asymmetric dimethylarginine (ADMA) in patients with schizophrenia, schizoaffective disorder, bipolar disorder, and depression were determined and compared to serum concentrations in healthy individuals. In all psychiatric diseases investigated, the ADMA concentration was elevated compared to the control group. Patients with recurrent depressive disorder had higher ADMA levels than patients with only one depressive episode. No differences between women and men were found. The elevated ADMA levels suggest that ADMA is involved in the pathophysiology of psychiatric diseases.

INTRODUCTION Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5-HTTLPR and SSRI serum concentrations. METHODS 49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly. RESULTS Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r² = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31). DISCUSSION In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials.

Introduction: The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) system activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA system activity. Methods: We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline. Results: Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment. Discussion: Our findings show IGF-I to be related to HPA system activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA system activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.

Introduction: Depression, stress and antidepressant treatment have been found to modulate the expression of growth factors. Methods: We studied depressed patients receiving randomized treatment with venlafaxine or mirtazapine for 28 days. Results: There was no significant difference between baseline VEGF concentrations in depressed patients compared to healthy controls. We found no significant effect of antidepressant treatment on serum VEGF. Discussion: In contrast to serum BDNF, VEGF may not be a suitable biomarker for effects of antidepressant treatment with venlafaxine or mirtazapine.

Depression, stress and antidepressant treatment have been found to modulate the expression of brain-derived neurotrophic factor (BDNF). Recent research suggests that serum BDNF concentration is reduced in depression and that antidepressant treatment leads to an increase in serum BDNF concentration. We studied depressed patients receiving a randomized antidepressant treatment with either mirtazapine (n=29) or venlafaxine (n=27) for 28 days in a prospective design. Changes in the concentrations of serum neurotrophins in response to antidepressant treatment were assessed. There was a significant “treatment” by “medication” interaction effect on BDNF serum concentrations that indicated a decline of BDNF in venlafaxine-treated patients (7.82±3.75–7.18±5.64 ng/mL), while there was an increase in mirtazapine-treated patients (7.64±6.23–8.50±5.37 ng/mL). There was a trend for a “treatment” by “remission” interaction with a favourable clinical course being related to increasing serum BDNF. Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant and potentially on the clinical course.

23 schizophrenic outpatients in maintenance treatment with zuclopenthixol decanoate were included in a study aimed at finding the minimum effective dose and corresponding serum concentration of zuclopenthixol. Every three months the dose was gradually reduced until prodromal symptoms appeared, indicative of an incipient relapse. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn to determine the serum concentration. This dose reduction principles proved feasible. Only one patient had a clear-cut relapse. The condition of the remaining patients was acceptably maintained by a dose increase. The minimum effective dose of zuclopenthixol was 200 mg/2 weeks (range 60-400), with a serum concentration of 22 nmol/l (7.1-69.7). There was a significant correlation between the administered dose and the corresponding serum level of the drug (r = 0.66, P < 0.01). A trend towards a positive correlation was found between the serum level at the minimum effective dose and the BPRS score (r = 0.42, P < 0.1). No correlation was found between the serum level and the side-effects or length of neuroleptic treatment. It is concluded that routine serum drug monitoring is hardly indicated in the long-term depot-neuroleptic treatment of schizophrenic patients. A strategy aiming at continually seeking the lowest effective dose on the basis of clinical parameters appears more appropriate, especially in case of depot-neuroleptic treatment.

INTRODUCTION The aim of this study was to relate drug concentrations in serum and clinical effects in patients treated with the new antidepressant duloxetine. METHODS Data were obtained from a newly established therapeutic drug monitoring (TDM) survey. Duloxetine was measured using HPLC with UV detection and clinical effects by the clinical global impressions (CGI) scale for improvement. RESULTS The study included 103 depressed inpatients (69% female). Patients under duloxetine monotherapy who were very much improved according to CGI had significantly (p

INTRODUCTION: There is no established relationship between the serum concentration of selective serotonin reuptake inhibitors (SSRIs) and clinical response in depressed patients. METHODS: We analyzed paroxetine concentrations in serum of 46 depressed patients during treatment with a fixed dosage of 40 mg paroxetine. RESULTS: After 5 weeks 29 patients responded to treatment, while 17 did not. Analysis of variance with repeated measures (ANOVA-rm) revealed a significant effect of "response" with responders having lower serum concentrations throughout the treatment period, when compared to non-responders. After 2, 3, and 4 weeks of treatment, we could define an upper threshold of paroxetine serum concentrations (week 1 : 22.7 ng/mL; week 2 : 43 ng/mL; week 3 : 53.4 ng/mL; week 4 : 39.1 ng/mL) above which response to treatment was unlikely. CONCLUSION: We conclude that -- in contrast to other pharmacological approaches -- high rather than low drug serum concentrations may be associated with non-response in paroxetine treatment of depressed patients.

The need to maintain long-term treatment of chronic pathologies makes the appearance of interactions possible when such therapies incorporate other drugs to deal with the aggravation of the same or other intercurrent pathologies. A case is presented in which the addition of trazodone to a chronic treatment with carbamazepine (CBZ) is associated with symptoms typical for intoxication by this antiepileptic, accompanied by a raised serum concentration. When the trazodone was suspended, these symptoms lessened and the concentration of CBZ decreased progressively, suggesting a probable interaction between the 2 drugs.

This study compared fluorescence polarization immunoassay (FPIA) with a high performance liquid chromatographic (HPLC) method from the point of view of their applicability to therapeutic drug monitoring of patients treated with clomipramine alone. Blood was withdrawn from 20 depressed inpatients (54 +/- 14 years) under steady state conditions. The FPIA determined total tricyclic antidepressant (TCA) concentrations with day to day variability below 11%. The automated HPLC method separated clomipramine, N-desmethylclomipramine, 8-hydroxyclomipramine and 8-hydroxydesmethylclomipramine with interassay coefficients of variance below 12%. The concentrations measured by FPIA were similar to HPLC results. Total TCA concentrations measured by FPIA and the sum of clomipramine and desmethylclomipramine measured by HPLC correlated significantly (r = 0.780 and p < 0.01). However, 40% of individual FPIA determinations yielded results that differed by more than 50% from the HPLC concentrations. Changes in clinical rates were related only to TCA serum concentrations that had been analyzed by HPLC. It is concluded that the semiquantitative FPIA is unsuitable for therapeutic drug monitoring in patients under clomipramine treatment, whereas the differential analysis of clomipramine and metabolites by HPLC is informative and can be used to improve the antidepressant drug treatment.

11 gesunde Probanden unterzogen sich 55 Einzelversuchen zum Zwecke vergleichender Untersuchungen an drei Lithiumpraparaten (Lithiumacetat = Quilonum®, Lithiumcarbonat retard = Quilonum retard® und Lithiumsulfat retard = Lithium-Duriles®). Eine Versuchsperson schied wegen Nebenwirkungen in Form von erheblicher Ubelkeit, Schwitzen und Erbrechen nach dem ersten Versuch aus. Nebenwirkungen in Abhangigkeit von der Dosishohe und der Anflutungsgeschwindigkeit wurden insgesamt bei 22 der 55 Versuche beobachtet; es handelte sich uberwiegend um Ubelkeit, Durchfalle und Mudigkeit. Bei einmaliger Gabe von 24 mval Lithium betrugen die Mittelwerte der Serumgipfel bei Lithiumacetat 0,95 mval, bei -carbonat retard 0,78 mval und bei -sulfat retard 0,64 mval, die entsprechenden Streubereiche erstrecken sich uber 0,71, 0,48 und 0,33 mval. Die Gipfelwerte hatten ihren Schwerpunkt bei Lithiumacetat nach einer Stunde, bei -carbonat retard nach 2 Stunden und bei -sulfat retard nach 3 Stunden. Der Abfall der Serumspiegel war relativ gleichformig, die Halbwertszeit lag zwischen 12 und 17 Stunden. Die geringere Streuung der erzielten Serumspiegel bei Lithiumsulfat retard trat bei hoherer Dosierung noch auffallender hervor: Die Lithiumausscheidung war bei den 3 Praparaten nach 48 Stunden nur geringfugig different: Mittelwerte von Lithiumacetat 82,5 %, von -carbonat retard 83,9 % und von -sulfat retard 80,6 %. Die retinierte Lithiummenge variierte bei den einzelnen Praparaten im Einzelfall regellos und nicht unerheblich. Zusatzliche Flussigkeitszufuhr fuhrte zu vorubergehender Beschleunigung der Ausscheidung innerhalb der ersten 12 Stunden. * Auszugsweise vorgetragen auf der 87. Wanderversammlung sudwestdeutscher Neurologen und Psychiater in Baden-Baden am 6.6.1971. 11 normal probands underwent 55 different tests in order to compare 3 lithium-preparations (lithium acetate in ordinary tablets, lithium carbonate and lithium sulphate, the latter two in sustained-release tablets). One proband had to be excluded after the first test because of side-effects in form of considerable nausea, sweating and vomiting. Side-effects dependent on the dosage and the velocity of increase of serum concentration have been observed in 22 of the 55 tests; they consisted predominantly in nausea, diarrhea and tiredness. After a single dose of 24 mval lithium the mean values of the maximum serum lithium concentrations were 0.95 mval for lithium acetate, 0.78 mval for lithium carbonate retard and 0.64 mval for lithium sulphate retard; the corresponding deviations were 0.71, 0.48 and 0.33 mval. The maximum values for lithium acetate were attained after 1 hour, for lithium carbonate retard after 2 hours and for lithium sulphate retard after 3 hours. The rate of fall of the serum levels was relatively constant, the half-elimination time was 12–17 hours. The little deviation of the serum lithium concentrations for lithium sulphate retard was still less after higher dosage. The lithium elimination after 48 hours differed only slightly in the 3 preparations; mean values for lithium acetate were 82.5 %, for lithium carbonate retard 83.9 % and for lithium sulphate retard 80.6 %. The lithium retention varied inconstantly and in singular cases not unconsiderably. Additional intake of fluid resulted in a temporary faster elimination within the first 12 hours.