Hans-Jürgen Möller

Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects

We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects.

Biochemical Findings of Negative Symptoms in Schizophrenia and Their Putative Relevance to Pharmacological Treatment

The most prominent biochemical finding in schizophrenic patients with negative symptoms appears to be the reduction in central dopaminergic, serotoner-gic and noradrenergic activity. This decrease in amine activity tends to be associated with structural brain abnormalities, i.e., cortical atrophy or enlarged ventricles. There are indications that typical neuroleptics reduce those negative symptoms of schizophrenia that are secondary to positive symptoms when these are effectively treated. However, negative symptoms of schizophrenia that occur independently of positive symptoms may also be reduced with monoamine oxidase inhibitors and atypical antipsychotic drugs, such as clozapine. The latter’s efficacy seems to be related to their pharmacological profile, i.e., their interference with dopaminergic, noradrenergic and seroto-nergic receptor systems and metabolism.

Plasma catecholamines and selective slow wave sleep deprivation.

The present study evaluated the effect of slow wave sleep (SWS) deprivation on plasma levels of catecholamines in healthy male volunteers. Eleven volunteers spent 4 nights in the sleep laboratory (2 nights of habituation and 2 further nights); during the latter, 1 night served as control, and in the other, SWS deprivation was performed. Blood was drawn at 30-min intervals. SWS was reduced by 86%; no sleep stage 4 was observed during the SWS-deprived nights. SWS reduction was found not to correlate with catecholamine levels. However, epinephrine levels were found to be sensitive to sleep fragmentation. The time interval between arousals in the SWS-deprived night as well as the difference in sleep efficiency were related to increases in epinephrine levels (p < 0.01 and p < 0.025, respectively). These results support the view that continuity rather than the duration of SWS is important for the recuperative value of sleep.

Evidence for a seasonal form of recurrent brief depression (RBD-seasonal)

We have established a relationship between recurrent brief depression (RBD) and seasonal affective disorder (SAD) in a cohort of 42 outpatients who presented themselves at a clinic for seasonal affective disorder at the Psychiatry Department of the University of Bonn, Germany. Our preliminary data indicate that 31% of the patients who were diagnosed as suffering from either SAD or its subsyndromal form (S-SAD) can also be categorized as RBD (RBD-seasonal) for a 1-year observation period. During the time span of 1 year, RBD-seasonal patients had a mean number of 20±9 episodes, which were accentuated in fall/winter, outnumbering the ones in spring/ summer significantly (P<0.001). The mean duration of each episode was 4.6±2.6 days in the RBD-seasonal group. RBD-seasonal patients experienced seasonal changes as more of a problem and reported a lower percentage of first-degree relatives with a history of depression than the non-RBD-seasonal group.

Hailey-Hailey disease and bipolar affective disorder in three members of the same family

Zusammenfassung. Wir berichten über eine Kosegregation von Morbus Hailey-Hailey (MHH) und bipolarer affektiver Erkrankung bei drei Mitgliedern einer Familie. Mit dem Fortschritt molekularbiologischer Techniken ist die Genlokalisation bei Erkrankungen mit einfachem Vererbungsmuster, wie dem autosomal-dominant vererbten MHH, eine Frage der Zeit. Die chromosomale Region des MHH-Gens wird dann auch Kandidatenregion für Kopplungsanalysen bei affektiven Erkrankungen sein.Summary. We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.

Orthostatic Challenge during Neuroleptic Test Dose: A Possible Predictor of Short-Term Outcome

Cardiovascular measurements were used as indicators of autonomic arousal during an orthostatic challenge test without medication and after a test dose of 150 mg perazine in 20 acute schizophrenic patients. Unmedicated schizophrenics showed elevated heart rates and elevated systolic and diastolic blood pressure in comparison to healthy volunteers. After a test dose of 150 mg perazine, responders (using BPRS outcome criteria after 23 days) showed a pronounced orthostatic heart rate reaction in comparison to nonresponders. Results are discussed in relation to arousal theories and central dopaminergic activity in schizophrenia.

Neuere Ergebnisse molekulargenetischer Untersuchungen bei psychotischen Erkrankungen

Der erste Schritt zur Aufklarung genetisch (mit) bedingter Erkrankungen besteht in der Lokalisation atiologisch relevanter Gene im Genom. Bei genetisch komplexen Erkrankungen, wie z. B. den Psychosen, kann nur die gleichzeitige Anwendung verschiedener Kartierungsstrategien zum Erfolg fuhren. Zwar konnte weder in Kopplungs- noch in Assoziationsstudien fur die Psychosen bisher ein Genort replizierbar lokalisiert werden. Trotzdem ist aufgrund der in den letzten Jahren erzielten Fortschritte bei anderen genetisch komplexen Erkrankungen damit zu rechnen, das auch bei den psychotischen Erkrankungen in der nachsten Zeit atiologisch relevante Gene lokalisiert werden konnen.