We report the case of a patient with major depression and obsessive-compulsive disorder who had simultaneously high serum citalopram, clomipramine, and alprazolam concentrations probably due to the reciprocal competitive inhibition of the cytochrome P450-catalyzed oxidative metabolism.

FK506 and rapamycin (Rap) are immunosuppressive drugs that act principally on T-lymphocytes. The receptors for both drugs are FK506-binding proteins (FKBPs), but the molecular mechanisms of immunosuppression differ. An FK506–FKBP complex inhibits the protein phosphatase calcineurin, blocking a key step in T-cell activation, while the Rap –FKBP complex binds to the protein kinase target of rapamycin (TOR), which is involved in a subsequent signalling pathway. Both drugs, and certain non-immunosuppressive compounds related to FK506, have potent antimalarial activity. There is however conflicting evidence on the involvement of Plasmodium calcineurin in the action of FK506, and the parasite lacks an apparent TOR homologue. We therefore set out to establish whether inhibition of the Plasmodium falciparum FKBP PfFKBP35 itself might be responsible for the antimalarial effects of FK506 and Rap. Similarities in the antiparasitic actions of FK506 and Rap would constitute indirect evidence for this hypothesis. FK506 and Rap acted indistinguishably on: (i) specificity for different intra-erythrocytic stages in culture, (ii) kinetics of killing or irreversible growth arrest of parasites and (iii) interactions with other antimalarial agents. Furthermore, PfFKBP35's inhibitory effect on calcineurin was independent of FK506 under a range of conditions, suggesting that calcineurin is unlikely to be involved in the antimalarial action of FK506.

Treatment-resistant depression (TRD) may be implicated in 33–57% of depression cases. The currently available effective treatments include electroconvulsive therapy (ECT) or augmentation of serotonin selective reuptake inhibitors (SSRIs) with antipsychotics. ECT and antipsychotics are both associated with safety and tolerability concerns. Depression is hypothesized to result from a dysregulation of monoamine neurotransmitters, although the source of the dysregulation has been unclear. However, recent studies have revealed that an enzyme that degrades the neurotransmitters, known as monamine oxidase-A (MAO-A), may be overactive in patients with depression. Thus, treatments for depression that modulate MAO-A could act upstream relative to current antidepressant treatments. Monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders. Some evidence suggests that MAOIs may act by reversing excessive neurotransmitter depletion within the neuron and the synapse. MAOIs tend to be underutilized in clinical practice, due in part to misinformation and mythology about their dietary and drug interactions. The new class of reversible monoamine oxidase inhibitors (RIMAs) has shown efficacy in depression, with safety and tolerability comparable to SSRIs. This article discusses recent progress in RIMAs toward the treatment of TRD. Dietary and drug interactions of MAOIs will be covered, as well as guidelines for integrating these agents into clinical practice.

Antidepressant treatments, including selective serotonin reuptake inhibitors, are associated in older adults with an increased risk of adverse effects compared to younger adults. This is partly explained by multiple drug use causing drug–drug interactions. In the present report, we describe a case of serotonin syndrome in an 88-year-old woman receiving a low dose of escitalopram. The onset of this episode could have been induced by a drug–drug interaction with an acute treatment by miconazole gingival adhesive tablets. The lack of pharmacokinetic data in the elderly population should prompt us to be especially cautious about prescription of this new formulation of miconazole in association with drugs metabolized by cytochromes P450 isoenzymes.

Summary

Background and objective: The aim of this prospective study was to compare the effect of the administration of desflurane or sevoflurane to a fixed neuromuscular block. Methods: After written consent, 12 patients were anaesthetized with propofol and sufentanil. Atracurium was administered via a continuous infusion in order to obtain 85% twitch depression of the control value assessed by repeated accelerometric stimulation at the adductor pollicis. Once stabilized over the course of 30 min, propofol was discontinued and either desflurane (n = 6) or sevoflurane (n = 6) was delivered at 1 MAC in a mixture of 50% O2 in air. Study parameters were the magnitude and the time of twitch height variations. Results are presented in mean ± SD. Result: Exposure to halogenated agents led to a significant reduction in twitch height with similar magnitude between the two agents. However, interaction with desflurane showed an initial and transient rise (35 ± 22%) in twitch height before subsequent depression occurred. The time to reach 50% of the signal depression in the desflurane group was significantly delayed (25 ± 7 vs. 11 ± 4 min in the sevoflurane group; P < 0.01). Conclusions: On a stable neuromuscular block elicited by continuous infusion of atracurium, the abrupt administration of desflurane or sevoflurane reduces the accelerometric responses of the adductor pollicis in a similar way. This potentiating effect is produced faster after sevoflurane than after desflurane. With desflurane, a biphasic effect (of a transient and moderate increase followed by depression of the signal) was recorded.

We report the case of a patient with schizophrenia who demonstrated increased serum clozapine and norclozapine levels in association with hypertension, when treated with fluoxetine and clozapine in combination.