# 04 - Caffeine intoxication # Caffeine intoxication Other substances CHAPTER 12 ■ ■The potential effects of caffeine on the metabolism of other drugs, as well as the potential to induce a caffeine withdrawal syndrome, should always be considered before substituting caffeine-­free drinks. Caffeine intoxication The DSM-­519 defines caffeine intoxication as the recent consumption of caffeine, usually in excess of 250mg, accompanied by five or more of the symptoms in Box 12.1. In caffeine intoxication, these symptoms cause significant distress or impairment in social, occupational or other important areas of functioning and are not due to a ­general medical condition or better accounted for by another mental disorder (e.g. an anxiety disorder). Caffeine abuse or dependence as a clinical syndrome has been reported3 and caffeine use disorder and caffeine withdrawal are both DSM-­5 diagnoses. Table 12.3  Interactions with caffeine. Interacting substance Effect Comments CYP1A2 inhibitors: Oestrogens Cimetidine Fluvoxamine (may decrease caffeine clearance by 80%)15 Disulfiram Reduce caffeine clearance Effects of caffeine may be prolonged or increased Adverse effects may be increased May precipitate caffeine toxicity Cigarette smoke* CYP1A2 inducer – increased caffeine metabolism6 Smokers may require higher doses of caffeine to gain desired effects6 Lithium High doses of caffeine may reduce lithium levels Caffeine withdrawal may cause a lithium level rise16 MAOIs May enhance stimulant CNS effects Clozapine Caffeine may increase clozapine plasma concentrations by up to 60%17 Thought to be via competitive inhibition of CYP1A2. Other drugs affected by caffeine-­induced inhibition of the enzyme include olanzapine, imipramine and clomipramine. SSRIs Large doses of caffeine may increase risk of serotonin syndrome18 Benzodiazepines Caffeine may act as an antagonist Caffeine reduces the efficacy of benzodiazepines8 * Vaping has no effect on CYP1A2 function. CNS, central nervous system; MAOIs, monoamine oxidase inhibitors.