Nicotine and symptoms of schizophrenia: the 2017 picture

Abstract

The tendency of people who suffer with schizophrenia to consume large amounts of cigarettes and to extract more nicotine from these cigarettes is well-known. A sizeable body of work investigating this has concluded that smoking in people with schizophrenia improves the dysfunctional sensory gating intrinsic to this disease. This has been recognised at least since the late 1980s. Consequently, the pro-cognitive effect of nicotine is now well-recognised and has led to the investigation of nicotinic receptor modulators as potential treatments for schizophrenia. Particular interest has focused on the treatment of negative symptoms in this illness. While there is a solid theoretical basis for this line of drug development, in practice, later-stage drug trials of compounds such as TC-5619 (bradanicline) in Phase 2 and EVP-6124 (encenicline) in Phase 3 have been disappointing. Numerous intolerable side-effects have been important in limiting the clinical use of such compounds. It is conceivable that the reason for intolerable side-effects might be a consequence of the wide distribution of nicotinic cholinergic receptors: α₇ nicotinic receptors are found in several cerebral areas, in the spleen and in lymphocytes at lymph nodes.

Later-stage drug development trials which reveal insurmountable administration problems are perhaps indicative of the great practical distance between theoretical recognition of a potential therapeutic agent and its eventual translational appearance in the armory against an illness.  Given that this is the case it may still be worthwhile to look at the simple administration of exogenous nicotine via e-cigarettes or chewing-gum as an adjunctive agent in the treatment of schizophrenia in the interim. More prosaically, the banning of smoking in many hospital premises in the UK has led to a difficulty in the practical management of acutely ill people with schizophrenia in the in-patient setting. In a group of people who are profoundly psychiatrically unwell, and often physically compromised to some degree because of their cigarette consumption, alternative management techniques for the latter must be explored.  Use of exogenous nicotine replacement in a less harmful delivery manner than cigarettes in a group of people who have a clear physiological reason for smoking -i.e. to increase their deficient endogenous cerebral nicotine levels – is worthwhile to investigate. Very recent work in exactly this direction has been undertaken. Nursing management of such patients may be greatly improved as a result, as may their on-going engagement with the therapeutic team. Here is an illustration of how theoretical considerations eventually come to have a pragmatic consequence in the day-to-day management of people with severe and enduring mental illnesses like schizophrenia.