Mania induced by antidepressants - characteristics and specific phenomena in children and adolescents. / Mania indukowana lekami przeciwdepresyjnymi ­ charakterystyka zjawiska u dzieci i mlodziezy.

The phenomenon of drug-induced mania, i.e., a manic episode associated with the use of pharmacotherapy (in particular antidepressants) is well defined and described in groups of adult patients. The negative effect on the course of bipolar disorder has been confirmed. In the group of children and adolescents, this subject is still poorly known and rarely described because of controversies in diagnosing early-onset bipolar disorder. The authors present an overview of current research on this problem starting from case reports, through open studies to randomized trials. Because the results of studies are ambiguous, the main problems that hinder the formulation of objective conclusions and the most important directions for further research are also discussed. The authors also present current hypotheses on the phenomenon of drug-induced mania in children and adolescents to systematize knowledge on the subject and provide diagnostic help in everyday clinical work. In agroup of children and adolescents, there is aneed to differentiate the phenomenon of drug-induced mania depending on the basic disorder, because similarly to studies that concern adult patients this problem seems to occur more frequently in patients with bipolar disorder than in other psychiatric disorders. It seems that the diagnosis of drug-induced mania is possible in children and adolescents at the present stage of knowledge, however, the assessment of the prevalence of this phenomenon requires careful evaluation in further studies.

Paliperidone LAI and Aripiprazole LAI Plasma Level Monitoring in the Prophylaxis of Bipolar Disorder Type I with Manic Predominance.

INTRODUCTION: The objective of this study was the evaluation of utility of plasma level monitoring in the clinical stabilizing efficacy and tolerability of paliperidone palmitate (PP) vs. aripiprazole monohydrate (AM) in bipolar disorder I (BD I) with manic predominance. METHODS: Fifty-six outpatients of both sexes, age ranging from 18 to 65 years, affected by BD I with manic predominance, orally treated and stabilized after acute episode for at least 2 weeks with paliperidone or aripiprazole (n=31, paliperidone; n=25, aripiprazole) underwent a prospective observational study of switching to the corresponding long-acting injection (LAI) on the basis of clinical evaluation. The efficacy and tolerability of the 2 treatments were assessed by BPRS, PANSS, HAMD21, and MRS rating scales and a check list every month for 12 months. Drug plasma levels determinations (PLs) were performed at the same times. RESULTS: A good clinical stability and tolerability of both drugs were reported. Lower mean PLs of PP showed a positive effect on depressive symptoms. AM PLs variability was associated with greater instability of manic symptoms whereas intermediate PLs seem to have more influence on depressive symptomatology. DISCUSSION: PLs drug monitoring has been proven to be useful, and further investigations to identify optimal therapeutic ranges for LAI formulations are needed.

Lithium attenuates d-amphetamine-induced hyperlocomotor activity in mice via inhibition of interaction between cyclooxygenase-2 and indoleamine-2,3-dioxygenase.

In the present study, we investigated whether mood stabilizer lithium (Li) protects against d-amphetamine (AMP)-induced mania-like behaviours via modulating the novel proinflammatory potential. Repeated treatment with AMP resulted in significant increases in proinflammatory cyclooxygenase-2 (COX-2) and indolemaine-2,3-dioxygenase-1 (IDO)-1 expression in the prefrontal cortex (PFC) of mice. However, AMP treatment did not significantly change IDO-2 and 5-lipoxygenase (5-LOX) expression, suggesting that proinflammatory parameters such as COX-2 and IDO-1 are specific for AMP-induced behaviours. AMP-induced initial expression of COX-2 (15 minutes post-AMP) was earlier than that of IDO-1 (1 hour post-AMP). Mood stabilizer Li and COX-2 inhibitor meloxicam significantly attenuated COX-2 expression 15 minutes post-AMP, whereas IDO-1 inhibitor 1-methyl-DL-tryptophan (1-MT) did not affect COX-2 expression. However, AMP-induced IDO-1 expression was significantly attenuated by Li, meloxicam or 1-MT, suggesting that COX-2 is an upstream molecule for the induction of IDO-1 caused by AMP. Consistently, co-immunoprecipitation between COX-2 and IDO-1 was observed at 30 minutes, 1, 3, and 6 hours after the final AMP treatment. This interaction was also significantly inhibited by Li, meloxicam or 1-MT. Furthermore, AMP-induced hyperlocomotion was significantly attenuated by Li, meloxicam or 1-MT. We report, for the first time, that mood stabilizer Li attenuates AMP-induced mania-like behaviour via attenuation of interaction between COX-2 and IDO-1, and that the interaction of COX-2 and IDO-1 may be critical for the therapeutic intervention mediated by mood stabilizer.