Quetiapine and norquetiapine serum concentrations and clinical effects in depressed patients under augmentation therapy with quetiapine.

BACKGROUND: Quetiapine has been recently approved as an add-on therapy in the treatment of major depressive disorders in the case of inadequate response to antidepressant monotherapy. Thereby the antidepressant potential is attributed to the N-demethylated metabolite norquetiapine (NQ). The aim of this cross-sectional analysis was to relate quetiapine (Q) doses to serum concentrations of Q and its active metabolite and clinical effects. METHODS: Data were obtained from patients who had been treated with different antidepressants and augmented under naturalistic conditions with Q for whom blood level measurements were requested. RESULTS: For this analysis, 105 depressed patients were included who had been augmented with Q. The mean daily doses of Q were 222 ± 125 mg. Doses correlated significantly (P < 0.001) with the highly variable serum concentrations of both Q and NQ. Median serum concentrations of Q and NQ were 46 ng/mL (25th to 75th percentile 20-91 ng/mL) and 59 ng/mL (25th to 75th percentile 26-133 ng/mL), respectively. Concentrations per dose ranged from 0.10 to 0.58 ng·ml·mg for Q and from 0.17 to 0.59 ng·ml·mg for NQ. Most patients (55%) received comedications in addition to the antidepressant drug and Q. According to the clinical global impressions scale, 60% of the patients were either much (36%) or very much improved (24%). Receiver-operating characteristic analysis revealed no significant differences of serum concentrations between responders and nonresponders for NQ (P = 0.835) but a trend for Q (P = 0.056). CONCLUSIONS: Due to marked variability of Q and NQ concentrations in the blood, therapeutic drug monitoring may be helpful to identify pharmacokinetic peculiarities. The lack of correlation between serum concentrations of NQ and clinical improvement casts doubts on the concept that NQ is the pharmacologically active principle for the augmentation therapy.

Therapeutic application of 20-kHz transcranial ultrasound in an embolic middle cerebral artery occlusion model in rats: safety concerns.

BACKGROUND AND PURPOSE: Therapeutic application of diagnostic ultrasound has been shown to improve recanalization rates in patients with acute cerebral vessel occlusion. There is experimental evidence that low-frequency ultrasound may be superior. This study was designed to evaluate the therapeutic efficacy and safety of low-frequency ultrasound in an embolic middle cerebral artery occlusion model in rats. A parameter setting was used that had not previously shown any side effects and interactions with healthy rat brain tissue. METHODS: Male Wistar rats were submitted to middle cerebral artery clot embolism and transcranial treatment with 20-kHz continuous-wave ultrasound (0.2 W/cm(2)), either alone or in combination with recombinant tissue-type plasminogen activator. Control groups received no treatment or recombinant tissue-type plasminogen activator alone. Outcome assessment consisted of determination of infarct volume and neurological evaluation. RESULTS: Eleven animals treated with ultrasound died during the follow-up period of 7 days, compared with 2 animals in the control groups (P=0.028). In 3 animals, subarachnoid hemorrhage was detected (1 in the control group). The other animals that died displayed secondary worsening after an initial period of normal vigilance. Histological examination revealed massive edema formation. In surviving animals, no benefit of treatment could be demonstrated. CONCLUSIONS: In this study, 20-kHz continuous-wave ultrasound caused death in a significant number of animals. Ultrasound at 20 kHz does not seem to be suitable for transcranial therapeutic cerebral application. The data underline the necessity to obtain further animal data to establish the safety limits of frequency and power output.

Involvement of jugular valve insufficiency in cerebral venous air embolism.

BACKGROUND: Cerebral venous air entrapment is a rare finding on cranial computed tomography (CT) scan. Peripheral air embolism is discussed as a potential cause. However, the mechanism of retrograde passage through internal jugular valves and veins is unclear. CASE REPORT: The case of a patient is reported, who had air entrapment in the left cavernous sinus. Prior to CT scanning, a peripheral intravenous line had been placed. Ultrasound revealed excessive insufficiency of the left internal jugular valve. To further study the mechanism of embolism, an echo contrast agent was injected into the cubital vein. A Valsalva maneuver resulted in retrograde transition of microbubbles across the insufficient valve. Valvular function on the unaffected right side was intact. CONCLUSIONS: This case report gives insight into the mechanism of cerebral venous air embolism. This is the firstcase describing jugular valve insufficiency as the missing link between peripheral air embolism and cerebral venous air entrapment.

[Delirium caused by nonconvulsive status epilepticus]. / Nonkonvulsiver Status epilepticus als Ursache eines Delirs.

We report about a patient (66 years) who was referred to our psychiatric hospital because of a progressive confusional state with acute onset. The colleagues of the referring psychiatric hospital considered a first manic episode as the cause of the symptoms and under therapy with haloperidol the confusional state had shown a progression.The clinical examination's findings were a mild central facial paresis on the right side and a mild hemiparesis on the right side with elevated reflex levels.The patient was disoriented, he had cognitive and mnestic deficits. His reasoning was slowed, incoherent and perseverating. The patient had a slight euphoria.An EEG recording showed a continuous regional EEG-seizure pattern. In combination with the clinical symptoms we diagnosed a nonconvulsive status epilepticus. Under anticonvulsive treatment with Lorazepam and Valproic acid the status epilepticus sustended but a control EEG recording showed signs of a Valproate-encephalopathy. Under treatment with Topiramate symptoms ameliorated but due to a vascular dementia the patient still showed fluctuating symptoms of cognitive and mnestic disturbances.