Paradoxical reaction

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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 pain caused by a pain relief medication.


Amphetamines a class of psychoactive drugs that are stimulants. Paradoxical drowsiness can sometimes occur in adults.[1]


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.[2] 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 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 but, especially in the case of suicide, may in at least some cases be merely due to differing rates of effect with respect to different symptoms of depression: If generalized overinhibition of a patient's actions enters remission before that patient's dysphoria does and if the patient was already suicidal but too depressed to act on his/her inclinations, the patient may find him/herself in the situation of being both still dysphoric enough to want to commit suicide but newly free of endogenous barriers against doing so.[3] Children and adolescents are more sensitive to paradoxical reactions of self-harm and suicidal ideation while taking antidepressants but cases are still very rare.[4]


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.[5]


Phenobarbital can cause hyperactivity in children.[clarification needed] This may follow after a small dose of 20 mg, on condition of no phenobarbital administered in previous days.[6] 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.


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.[7] Severe behavioral changes resulting from benzodiazepines have been reported including mania, schizophrenia, anger, impulsivity, and hypomania.[8]

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.[9]

Paradoxical effects of benzodiazepines appear to be dose related, that is, likelier to occur with higher doses.[10]

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.[11]

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.[12]

Benzodiazepines can sometimes cause a paradoxical worsening of EEG readings in patients with seizure disorders.[13]


  1. ^ Tecce JJ, Cole JO (1974). "Amphetamine Effects in Man: Paradoxical Drowsiness and Lowered Electrical Brain Activity (CNV)". Science Magazine. 185 (4149): 451–453. doi:10.1126/science.185.4149.451. Archived from the original on 2018-01-07. Retrieved 2018-01-07.
  2. ^ Eagle H, Musselman AD (July 1948). "The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms". J Exp Med. 88 (1): 99–131. doi:10.1084/jem.88.1.99. PMC 2135799. PMID 18871882.
  3. ^ Teicher MH, Glod C, Cole JO (February 1990). "Emergence of intense suicidal preoccupation during fluoxetine treatment". Am J Psychiatry. 147 (2): 207–10. doi:10.1176/ajp.147.2.207. PMID 2301661.
  4. ^ King RA, Riddle MA, Chappell PB, et al. (March 1991). "Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment". J Am Acad Child Adolesc Psychiatry. 30 (2): 179–86. doi:10.1097/00004583-199103000-00003. PMID 2016219.
  5. ^ Chlorpromazine - Adverse Effects- Behavioral Reactions[dead link]
  6. ^
  7. ^ Bramness JG, Skurtveit S, Mørland J (June 2006). "Flunitrazepam: psychomotor impairment, agitation and paradoxical reactions". Forensic Sci. Int. 159 (2–3): 83–91. doi:10.1016/j.forsciint.2005.06.009. PMID 16087304.
  8. ^ Cole JO; Kando JC. (1993). "Adverse behavioral events reported in patients taking alprazolam and other benzodiazepines". The Journal of Clinical Psychiatry. 54 (Suppl:49–61): 62–3. PMID 8262890.
  9. ^ Senninger JL; Laxenaire M. (1995). "[Violent paradoxal reactions secondary to the use of benzodiazepines]". Annales médico-psychologiques. 153 (4): 278–81. PMID 7618826.
  10. ^ Mancuso, Carissa E.; Tanzi, Maria G.; Gabay, Michael (September 2004). "Paradoxical Reactions to Benzodiazepines: Literature Review and Treatment Options". Pharmacotherapy. 24 (9): 1177–1185. doi:10.1592/phco.24.13.1177.38089. PMID 15460178. Archived from the original on 2012-12-13. Retrieved 2007-04-18.
  11. ^ "Letter: Tranquilizers causing aggression". British Medical Journal. 1 (5952): 266. February 1, 1975. doi:10.1136/bmj.1.5952.266. PMC 1672080. PMID 234269.
  12. ^ Berman ME, Jones GD, McCloskey MS (February 2005). "The effects of diazepam on human self-aggressive behavior". Psychopharmacology. 178 (1): 100–6. doi:10.1007/s00213-004-1966-8. PMID 15316710.
  13. ^ Perlwitz R; Grimmberger E; Schmidtsdorf R (June 1980). "[Immediate effect of intravenous clonazepam on the EEG]". Psychiatr Neurol Med Psychol (Leipz). 32 (6): 338–44. PMID 7403357.