Mental, neurological and substance use disorders (MNS) constitute 13% of the global disease burden, surpassing both cardiovascular diseases and cancers. Major depressive disorder (MDD) and schizophrenia are among the three most disabling MNS illnesses worldwide. The contribution of chronic inflammation to major mental disorders has received increased attention in the last decade, which revealed a host of pharmacological targets. Multiple recent reviews clearly demonstrate that schizophrenia is associated with a dysregulation of immune responses, as reflected by the observed abnormal profiles of circulating pro- and anti-inflammatory cytokines in affected patients. Moreover, some anti-inflammatory drugs have shown their effectiveness in the treatment of schizophrenia. Anti-inflammatory drugs have shown effectiveness in major psychiatric disorders, especially major depressive disorder (MDD) and schizophrenia. Four major classes of anti-inflammatory drugs have been studied to date: polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. We discuss the positive results of PUFAs in MDD, the mixed results for COX-2 specific inhibitors and minocycline in schizophrenia, and the positive preliminary data on aspirin and n-acetyl-cysteine. Adjunctive aspirin was shown to significantly improve psychotic symptoms in schizophrenia, but only two randomized controlled trials were carried out to date. Anti-TNFalpha showed also important effectiveness in resistant MDD with blood inflammatory abnormalities, which may highlight potential biomarkers of interest. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD or schizophrenia. If used with caution, they may be reasonable therapeutic alternatives for resistant symptomatology.

This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional. The proinflammatory cytokines, in addition to activating the hypothalamic–pituitary–adrenal axis and thereby increasing cortisol synthesis, also activate the tryptophan–kynurenine pathway. This results in the synthesis of the neurotoxic N-methyl-d-aspartate (NMDA) glutamate agonist quinolinic acid and 3-hydroxykynurenine thereby enhancing oxidative stress and contributes to neurodegeneration which characterise major depression particularly in late life.While antidepressants attenuate some of the endocrine and immune changes caused by inflammation, not all therapeutically effective antidepressants do so. This suggests that drugs which specifically target the immune, endocrine and neurotransmitter systems may be more effective antidepressants.The preliminary clinical evidence that some non-steroidal anti-inflammatory drugs, such as the cyclooxygenase 2 inhibitor celecoxib, can enhance the response to standard antidepressant treatment is therefore considered and a critical assessment made of the possible limitations of such an approach to novel antidepressant development.

Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Background and objective: Previous studies have shown that general anaesthetic agents modulate the production of hypothalamic prostaglandins (PG) D2 and E2, which are mediators of sleep and wakefulness respectively. Although flurbiprofen, a cyclo-oxygenase inhibitor, is used clinically as a non-steroidal anti-inflammatory agent and postoperative analgesic, it reduces prostaglandin production. Thus, this agent may affect the depth of sedation during general anaesthesia. In this study, we examined if flurbiprofen affects the bispectral index, which correlates with sedation levels.

Methods: Fifteen patients who underwent elective surgery under total intravenous anaesthesia with propofol and fentanyl were studied. The sedation level was monitored using a bispectral index monitor. On attainment of stable haemodynamics and a bispectral index, patients were given flurbiprofen axetil 50 mg intravenously. A bispectral index and 95% spectral edge frequency were recorded before and 5, 10, 15, 20 and 30 min after flurbiprofen axetil intravenously.

Results: Bispectral indexes of 51.7 (95% CI: 47.3–56.8), 51.7 (47.1–56.3), 51.3 (46.3–56.3), 50.3 (45.8–54.2), 48.9 (43.6–54.1) and 50.3 (45.5–55.2) at 0, 5, 10, 15, 20, 30 min after flurbiprofen axetil intravenously were observed. There was no change in this or 95% spectral edge frequency.

Conclusions: Clinical dose of flurbiprofen axetil does not alter the bispectral index and 95% spectral edge frequency under total intravenous anaesthesia with propofol and fentanyl.