Paradoxical effect

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

An example of a paradoxical reaction is when a pain relief medication causes an increase in pain.

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. The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior and symptoms sometimes misdiagnosed as psychosis.[1] Some sedatives prescribed for adults actually cause hyperactivity in some children.

Benzodiazepines

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.[2] Severe behavioral changes resulting from benzodiazepines have been reported including mania, schizophrenia, anger, impulsivity, and hypomania.[3]

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.[4]

Paradoxical effects of benzodiazepines appear to be dose related, that is, likelier to occur with higher doses.[5]

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.[6]

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.[7]

Benzodiazepines can sometimes cause a paradoxical worsening of EEG readings in patients with seizure disorders.[8]

Barbiturates

Phenobarbital can cause hyperactivity in children. This may follow after a small dose of 20 mg, on condition of no phenobarbital administered in previous days.[9] Prerequisity for this reaction is a continued sense of tension. The mechanism of action is not known, but it may be started by the anxiolytic action of the phenobarbital.

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.[10]

Antidepressants

Antidepressants can rarely 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.[11] Children and adolescents are more sensitive to paradoxical reactions of self-harm and suicidal ideation while taking antidepressants but cases are still very rare.[12]

Antibiotics

The paradoxical effect or Eagle effect (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.[13] Initially when an antibiotic agent is added to a culture media, the number of bacteria that survive drops, as one would expect. But after increasing the concentration beyond a certain point, the number of bacteria that survive, paradoxically, increases.

References

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