Low frequency rTMS as an add-on antidepressive strategy: heterogeneous impact on 99mTc-HMPAO and 18 F-FDG uptake as measured simultaneously with the double isotope SPECT technique. Pilot study.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are examination procedures that have shown that repetitive transcranial magnetic stimulation (rTMS) is biologically active. The aim of the present study was to investigate the patterns of regional cerebral 18F-fluorodeoxyglucose (18F-FDG) uptake and regional 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) uptake simultaneously during a series of therapeutic rTMS at low frequency. Four drug-resistant depressed patients underwent 10 rTMS as an add-on measure over 14 days. One day before and one day after TMS, simultaneous measurements of 18F-FDG, representing regional cerebral metabolic rate (rCMR), and 99mTc-HMPAO, representing regional cerebral blood flow (rCBF), were carried out. A conventional double head SPECT camera with 511 keV collimators was used. Statistically significant simultaneous overall changes of rCBF and rCMR were found in the upper prefrontal regions bilaterally in terms of increased uptake rates and in the left gyrus frontalis inferior in terms of decreased uptake rates of both isotopes compared to controls. Although this method improves our understanding of rTMS mechanism, there are limitations due to the lower resolution provided. Therapeutic rTMS seems to influence distinct, cortical regions affecting rCBF and rCMR.

A case of pharmacokinetic interference in comedication of clozapine and valproic acid.

In 4-6% of treatment histories, clozapine induces generalized seizures by reducing the seizure threshold. Despite the knowledge of high risks combined therapy (such as bone marrow suppression, pathological EEG changes), some authors even suggest the prophylactic combination with anticonvulsants in high dose treatment of clozapine. We report a case of a 33-year-old female patient, a heavy smoker, suffering from mixed schizoaffective disorder from 1989 onwards. At her 8th admission in 1998, she was rehospitalized after experiencing her first generalized seizure under clozapine treatment, although no seizure phenomenon or other relevant side-effects under several previous clozapine therapies had been observed. Therefore, she received a valproic acid co-medication during her clozapine therapy. Based on therapeutic drug monitoring of clozapine (weekly) under compliance-controlled conditions, the serum levels of clozapine significantly decreased, probably induced by valproic acid. According to the literature, this case report might support the clinical relevance of therapeutic drug monitoring when clozapine therapy is combined with valproic acid as co-medication.

Combining nefazodone and midazolam during ECT.

We report the case of a patient suffering from dysthymia. He underwent successful ECT treatment and was medicated with nefazodone and midazolam. Comparing the EEG and motor seizure duration in the periods with and without midazolam, no significant differences were recorded, but the dosage of thiopental and of succinylcholine had to be increased markedly after midazolam was discontinued (P < 0.05; ANOVA). This case indicates a substantial pharmacodynamic interaction between nefazodone, midazolam, thiopental, and succinylcholine.