A paradoxical reaction (or paradoxical effect) is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication.
Substances
Amphetamines Amphetamines are a class of psychoactive drugs that are stimulants. Paradoxical drowsiness can sometimes occur in adults. Research from the 1980s popularized the belief that ADHD stimulants such as amphetamine have a calming effect in individuals with ADHD, but opposite effects in the general population. Research in the early 2000s, however, disputes this claim, suggesting that ADHD stimulants have similar effects in adults with and without ADHD.
Antibiotics The paradoxical effect or Eagle effect (named after Harry 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 one would expect. But after increasing the concentration beyond a certain point, the number of bacteria that survive, paradoxically, increases.
Antidepressants
In a minority of cases, antidepressants can lead to violent thoughts of suicide or self-harm, as observed in some patients during and after treatment, which is in marked contrast to their intended effect. A 1991 study found that children and adolescents were more sensitive to paradoxical reactions of self-harm and suicidal ideation while taking fluoxetine (commonly known as Prozac).
Antipsychotics
Chlorpromazine, an antipsychotic and antiemetic drug which is classed as a "major" tranquilizer, may cause paradoxical effects such as agitation, hallucinations, excitement, insomnia, bizarre dreams, aggravation of psychotic symptoms and delirium. These may be more common in elderly dementia patients. The apparent worsening of dementia may be due to the anticholinergic side effects of many antipsychotics.
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. Barbiturates such as pentobarbital have been shown to cause paradoxical hyperactivity in an estimated 1% of children, who display symptoms similar to the hyperactive-impulsive subtype of attention deficit hyperactivity disorder. Intravenous caffeine administration can return these patients' behavior to baseline levels. A case report proposes a high rate (10-20%) of paradoxical response to anesthesia in ADHD patients, though this has not been objectively corroborated in controlled studies.
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 behavior. Severe behavioral changes resulting from benzodiazepines have been reported including mania, hypomania, psychosis, anger and impulsivity. 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. 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 medication 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. 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. Benzodiazepines can sometimes cause a paradoxical worsening of EEG readings in patients with seizure disorders.
Caffeine Caffeine is believed by many to cause paradoxical calmness or sedation in individuals with ADHD. There is insufficient evidence to determine if sedation caused by caffeine is due to a true paradoxical reaction, or rather from dehydration and sleep deprivation caused by the caffeine. Furthermore, there are no conclusive studies showing a differential effect of caffeine in individuals with ADHD compared to the general population.
Naltrexone Naltrexone blocks the opioid receptors, acting opposite to most opioid pain medications. It can be used to negate the effects of opioid painkillers. At doses around one-tenth of the typical dose, naltrexone has been used for pain relief. Low-dose naltrexone is believed to have an anti-inflammatory effect. This is an off-label use and not widely accepted by the medical and scientific community.
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