Paradoxical reaction

A paradoxical reaction or paradoxical effect is when medical treatment, usually a drug, has the opposite effect to that which would normally be expected.

An example of a paradoxical reaction is when a pain relief medication causes an increase in pain. Some sedatives prescribed for adults actually cause hyperactivity in children.

Benzodiazepines

For example, there are serious complications occurring in conjunction with the use of sedatives creating a series of effects in some people, that are the total opposite of those expected. Malcolm Lader at the Institute of Psychiatry in London estimates the incidence of these adverse reactions at about 5%, even in short-term use of the drugs. The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior and symptoms sometimes misdiagnosed as psychosis. Benzodiazepines, a class of psychoactive drugs called the "minor" tranquilizers, have varying hypnotic, sedative, anxiolytic, anticonvulsant, and muscle relaxing properties, but they may create the exact opposite effects. Susceptible individuals may respond to benzodiazepine treatment with an increase in anxiety, aggressiveness, agitation, confusion, disinhibition, loss of impulse control, talkativeness, violent behavior, and even convulsions. Paradoxical adverse effects may even lead to criminal behaviour. Severe behavioral changes resulting from benzodiazepines have been reported including mania, schizophrenia, anger, impulsivity, and hypomania. Self aggression has been reported and also demonstrated in laboratory conditions in a clinical study. Diazepam was found to increase people's willingness to harm themselves. Paradoxical effects of benzodiazepines appear to be dose related, that is, likelier to occur with higher doses. In a letter to the British Medical Journal, it was reported that a high proportion of parents referred for actual or threatened child abuse were taking drugs at the time, often a combination of benzodiazepines and tricyclic antidepressants. Many mothers described that instead of feeling less anxious or depressed, they became more hostile and openly aggressive towards the child as well as to other family members while consuming tranquilizers. The author warned that environmental or social stresses such as difficulty coping with a crying baby combined with the effects of tranquilizers may precipitate a child abuse event. Benzodiazepines can sometimes cause a paradoxical worsening of EEG readings in patients with seizure disorders.

Paradoxical rage reactions due to benzodiazepines occur as a result of an altered level of consciousness, which generates automatic behaviors, anterograde amnesia and uninhibited aggression. These aggressive reactions may be caused by a disinhibiting serotonergic mechanism.

Antipsychotics

Chlorpromazine, an antipsychotic and antiemetic drug, which is classed as a "major" tranquilizer may cause paradoxical effects such as agitation, excitement, insomnia, bizarre dreams, aggravation of psychotic symptoms and toxic confusional states.

Antidepressants

Antidepressants can sometimes make users obsessively violent or have suicidal compulsions, which is in marked contrast to their intended effect. This can be regarded as a paradoxical reaction. Children and adolescents are particularly sensitive to paradoxical reactions of self harm and suicidal ideation while taking antidepressants.

Antibiotics

The paradoxical effect or Eagle phenomenon (named after H. Eagle who first described it) refers to an observation of an increase in survivors, seen when testing the activity of an antimicrobial agent. Initially when an antibiotic agent is added to a culture media, the number of bacteria that survive drops, as you would expect. But after increasing the concentration beyond a certain point, the number of bacteria that survive, paradoxically, increases.

One of the explanations could be that as the concentration is too high, the agent might be self-antagonising the receptor with which it binds. (Penicillin binding proteins, for example, in the case of a penicillin.) This self antagonism, is only a possible explanation for the phenomenon. Another explanation could be that the antimicrobial agent precipitates out of solution, so activity is either not seen, or that the colorimeter is detecting crystals of antimicrobial.