Drug-induced behavioural disinhibition - Incidence, mechanisms and therapeutic implications

Behavioural disinhibition implies the loss of restraint over some form of social behaviour. Such disinhibition can be drug induced and, on rare occasions, lead to extreme acts of aggression or violence. Examples of behavioural disinhibition are often considered paradoxical and rare reactions to drugs, but they may in fact be a more severe behavioural manifestation of a general effect that the drug has on emotions and behaviour. However, the incidence of drug-induced behavioural disinhibition varies considerably and cannot be estimated accurately, as accounts stem mainly from case reports rather than from controlled clinical trials. Adverse effects of drugs are rarely, if ever, the sole focus of clinical studies, although they are now monitored more rigorously in controlled trials. There are numerous anecdotal case reports in the literature of behavioural disinhibition occurring during administration of benzodiazepines, and recent controlled trials have addressed this issue. The incidence varies with the population studied, but tends to be higher in patients with pre-existing poor impulse control. Alcohol (ethanol) potentiates the disinhibiting effect of benzodiazepines. Aberrant forms of disinhibited behaviour may be accompanied by memory loss. Disinhibition has also been reported after treatment with tricyclic antidepressants, and reports are now appearing that describe disinhibition in patients who have been treated with selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors. These include incidents of akathisia, suicidal urges, agitation, hyperactivity and mania. They are more prevalent in children and those with learning disabilities. Disinhibition is rare with antipsychotics and non-benzodiazepine anticonvulsants but some isolated case reports contain descriptions of such reactions with newer compounds. The most important drug variable in drug-induced behavioural disinhibition is dosage, although mode of administration is also important. Discontinuation of the drug is usually expected to resolve behavioural reactions, but in certain cases drug withdrawal may precipitate a reaction. In order to minimise drug-induced behavioural disinhibition, it is essential to always use the minimum dosage necessary, to increase the dosage gradually and to monitor the effects carefully. Multiple drug use should be avoided whenever possible.