Caffeine. cognitive and physical performance enhancer or psychoactive drug?

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases

Neurovascular and neuroinflammatory mechanisms associated with mood disorders

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Neuroinflammation and excitatory symptoms in bipolar disorder

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Antipsychotic and antiepileptic drugs in bipolar disorder: The importance of therapeutic drug monitoring

Bipolar disorder (BD) is a long-term illness with mood swings which are characterized by recurrent episodes of mania/hypomania and depression, with variable interpolations of relatively asymptomatic periods, called euthymic, in which, however, some psychopathological symptoms may persist. Although mood stabilizers, such as lithium, are the first-line treatment for the prevention of new BD episodes, combination therapy has become the standard of care for BD patients. Besides lithium, the use of a mood stabilizer along with an atypical antipsychotic is recommended in many patients. Recently, atypical antipsychotics (quetiapine, olanzapine, risperidone and aripiprazole) and antiepileptic agents (valproate, lamotrigine and oxcarbazepine) are increasingly used as mood stabilizers. To reduce side effects and optimize treatment it is important to perform accurate monitoring of drug blood levels in these patients, who are often treated with multiple drugs. Therapeutic drug monitoring (TDM) is in fact a powerful tool that, starting from clinical-chemical correlation data, allows to tailor-cut treatment to the specific needs of individual patients; hence the need to have reliable analytical methods available for the determination of plasma levels of drugs and their metabolites. Analyses of biological samples are mainly carried out using high-performance liquid chromatography (HPLC) coupled with different detectors, capillary electrophoresis and gas-chromatography. Various procedures are employed to remove biological interferences before analyzing the samples. This review focuses on currently available analytical TDM methods for atypical antipsychotics and antiepileptic agents used in the treatment of patients with bipolar disorder. Advantages and limitations of the various analytical methods will be reviewed and discussed, together with an evaluation of the role of TDM. © 2009 Bentham Science Publishers Ltd

Early clinical predictors and correlates of long-term morbidity in bipolar disorder

OBJECTIVES: Identifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). METHODS: We analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. RESULTS: Total % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. CONCLUSIONS: Long-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity

Melancholia agitata and mixed depression

OBJECTIVE: The diagnostic entity of major depressive episode includes both simple and agitated or mixed depression. Mixed depression is characterized by a full depressive episode with several symptoms of excitatory nature. Mixed depressions worsen if treated with antidepressants. METHOD: We have reviewed the clinical charts of the 2141 patients treated at the Centro Lucio Bini of Rome from January 1999 to June 2006. These patients were diagnosed according to DSM-IV criteria. Research diagnostic criteria were applied for agitated depression with motor agitation and Author's diagnostic criteria for agitated depression without motor agitation. RESULTS: One thousand and twenty-six patients had a depressive episode as index episode. Three hundred and forty six (33%) were mixed depressive states. One hundred and thirty eight (44%) of them were spontaneous; in 173 cases, the onset of the mixed depression was associated with antidepressants. CONCLUSION: Psychic and motor agitation are considered equally important for the definition of agitated depression. Treating agitated depression with antidepressants worsens the clinical picture. The use of Electroconvulsive Therapy (ECT), neuroleptics and anticonvulsants are recommended. The term Melancholia Agitata is proposed for agitated (mixed) depression

Which comes first? New insights on comorbidity between eating disorders and bipolar disorders.

Abstract Aims : Bipolar disorders (BDs) and eating disorders (EDs) are both common and severe mental illness and present wide areas of symptomatological overlap. The present study aims to focus on the most significant aspects of this comorbidity. Methods This review summarizes epidemiology, aethiopathology, prognostic impact, assessment, treatment of comorbidity between BDs and EDs, and comorbidity between bipolar or eating disorders and other psychiatric disorders. We have reviewed articles published in PubMed/Medline, Scopus, Embase, ScienceDirect from 2005 to 2020 concerning comorbidity between eating and bipolar disorders, and systematic reviews or metanalysis on comorbidities between EDs or BDs and other psychiatric disorders. Results Studies that specifically evaluate the prevalence of EDs in patients with bipolar disorder are more than the studies that investigate the opposite. In BDs, binge eating disorder (BED) represents the most common eating disorder with a prevalence ranging from 8,8% to 28,8%, whereas BN has a prevalence ranging from 4,8% to 10%, and AN from 1% to 7,4%. Instead, in ED patients, prevalence of bipolar disorders ranges from 11,5% to 68.1%. The relationship between EDs and BDs has not been yet investigated enough and consequently has not been totally understood. The presence of EDs has been considered as a marker of clinical severity in patients with bipolar disorders, whereas the presence of bipolar disorder in patients with EDs seems not to have a considerable effect on the age at onset of ED symptoms and on their severity. Comorbidities between EDs or BDs and other psychiatric disorders were also examined. Discussion Given the strong co-occurrence of eating and bipolar disorder, the treatment for one of these should consider that the other one may co-exist, and therefore should focus on both of them. In patients suffering from one of these disorders, the early screening for the other one should be made. As for pharmacological treatment, it is mandatory to consider that pharmacological treatment effective for one of the two disorders could worsen symptoms of the other, for instance many psychotropic medications could cause weight gain. Further studies are needed to reach an early diagnosis through the development of screening tools, and to deepen aspects of this comorbidity that remain still unknown with particular regard to pharmacological treatment and to biopsychological aspects that might be useful in determining the aetiopathology