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quinolones , one of the commonly used broad spectrum antibacterials , are frequently associated with neuropsychiatric adverse effects .
these may range from dizziness , headache , and sleep disturbances being the frequent ones , anxiety , suicidal ideations , delirium , hallucinations , agitation , confusion , psychosis , and catatonia being the other severe adverse events .
psychiatric adverse events in the form of manic reactions due to quinolones had been mostly reported to the food and drug administration ( fda ) and the world health organization ( who ) without sufficient clinical details , as well as validity of their diagnosis .
mania secondary to typhoid , dengue , and other febrile conditions have also been reported in literature .
typhoid fever has been shown to be associated with a range of neuropsychiatric manifestations with delirium being the most common presentation anteceding or occurring concomitantly with the fever mania is reported rarely .
we report a case of recurrent mania , which developed each time , the patient was exposed to quinolone antibiotics .
ad is a 34-year - old homemaker , who previously , had two manic episodes with no family history of mental illness / bipolar affective disorder .
she was not treated for the first episode and remitted within 1 month of the treatment with olanzapine 10 mg / day , and lithium carbonate 600 mg / day for the second episode .
the index episode started in february 2014 when she developed fever , nausea , and vomiting acutely .
she took paracetamol 500 mg orally with which fever subsided for once , but it recurred after 2 days and did not remit despite taking antipyretics further .
she consulted a physician after 1 week of onset of fever ( 10 day ) who diagnosed her with typhoid fever on the basis of serological investigations only ( widal test positive ; titers for agglutinin o > 1:160 and agglutinin h > 1:160 ) ; prescribed her oral ciprofloxacin 500 mg twice a day for a week .
fever subsided within the next 2 days , and she was asymptomatic for the next 5 days when vomiting and diarrhea recurred along with headache .
ciprofloxacin was continued for 1 more week . though above mentioned symptoms remitted in the next 2 days ,
she was noted to get up early in the morning ; would bath early and then start doing household chores .
she became more active , indulged herself into multiple tasks at the same time , and left them incomplete .
her family reported her to be very cheerful , amusing , and jocular which was unlike her previous self .
she increasingly participated in religious activities , indulged in unnecessary buying of clothes and jewellery .
she took ciprofloxacin for 4 more days in that week . despite stopping the medication , thereafter no improvement was noted . in the next 2 weeks
there was no history of altered sensorium , disorientation , and any perceptual abnormalities . as she became unmanageable
her general physical examination did not reveal any abnormality suggestive of either metabolic disorder or cerebrovascular disease .
she was not receiving any other medications nor did she abuse any psychotropic substances such as cocaine or amphetamines .
she was treated with olanzapine 10 mg and lithium carbonate 600 mg / day which was later on increased to 800 mg / day to achieve optimum serum lithium level .
she achieved complete remission within 6 weeks . in her past , she had suffered from gastroenteritis at 45 occasions but sought treatment only on two occasions .
these two episodes of gastroenteritis , which occurred 10 and 8 years back , were treated with ciprofloxacin and ofloxacin , respectively , but prescriptions were not available . on both occasions , she developed similar set of mental symptoms as in the index episode characterized by elated mood , decreased need for sleep , increased goal - directed activity , increased religiosity , over - talkativeness , and increase in goal - directed activities though severity were less .
hence , the diagnosis of medication - induced recurrent mania as per diagnostic and statistical manual of mental disorders fifth edition was kept .
the patient and family members were cautioned for the use of quinolones in future as these were implicated as etiological in her mental illness .
krauthammer and klerman gave the concept of mania occurring in association with physical disorders , medications , and drugs of abuse which was labeled as secondary mania .
an analogy to medical syndromes of multiple etiologies such as hypertension ( essential vs. secondary ) and parkinsonism ( idiopathic vs. secondary ) have also been drawn .
although the etiological dichotomy and validity of manic syndromes into primary versus secondary have been given on the basis of ( 1 ) close temporal association with an organic insult , ( 2 ) onset at a later age , ( 3 ) predominantly negative family history , and ( 4 ) negative premorbid history but we are still far from exact neurobiological etiology .
since the work of krauthammer and klerman , there have been many reports of secondary mania due to various etiologies . without going into literature review of secondary mania ,
we here give the common causes of this syndrome which include medications ( corticosteroids , isoniazid , levodopa , antibacterials , thyroxine , sympathomimetic drugs , chloroquine , baclofen , captopril , amphetamine , phencyclidine , and various anti - depressants ) , infectious diseases ( such as viral encephalitis ) , metabolic ( hemodialysis ) , intracranial neoplasms ( meningioma ) , temporal lobe epilepsy , and head injury .
the occurrence of mania has been reported in typhoid fever as well as with the use of a range of antibiotics , quinolones being the most notorious . however , typhoid fever as an etiological factor for manic reactions is not very commonly reported . in one of the previous case reports of mania in typhoid fever ,
the patient was afebrile at the time of onset of manic symptoms but was receiving ciprofloxacin , while in other case there were many other confounding factors , thus making it difficult to tease out the causative agent for hypomanic symptoms . in a retrospective review of the neuropsychiatric manifestations in 959 patients with typhoid fever ,
no case of mania was reported . on the other hand , mania in relation to antibiotics
103 cases were found in un-/published literature with the quinolone group of antibacterials being implicated as the causative agent in 48 ( 46.7% ) cases . in another recent review of adverse drug reactions of quinolones ,
mania was reported most frequently and in association with the use of ciprofloxacin probably due to its wider use . both of these reviews relied on the data provided by the fda and who , which in turn reported these adverse drug reactions during postmarketing surveillance .
although the mechanism of antibacterials leading to mania is unclear , the proposed hypothesis is their interactions with neurotransmitters , but competitive inhibition of gamma - aminobutyric acid receptors and induced epileptogenic neurotoxicity is suggested with reference to quinolones .
, there was temporal relationship of onset of mania with use of quinolones in all the episodes and in addition to typhoid fever for the current episode .
for the first two episodes , there was no fever , and information of the use of quinolones was only available from the caregiver .
in addition , there are no reports of mania in gastroenteritis . however , in the current episode both the laboratory evidence of typhoid fever and prescription of ciprofloxacin were medically documented . by the time ,
the patient developed mania her fever had subsided and thus only ciprofloxacin can be incriminated as the causative agent . although there are some pointers that establish the association of manic syndrome with the use of quinolones in the form of ( 1 ) occurrence of mania following quinolone use , ( 2 ) negative family history , ( 3 ) no independent manic reactions premorbidly ( if the previous two episodes are also attributed to the use of quinolones ) ; however , there is no definitive test to establish the specificity and strength of association which is a major limitation .
another limiting factor in this report is the lack of documented evidence of prior quinolone use and our reliance on the arbitrament of the caregiver .
antibiotics are one of the commonly used drugs at each level of healthcare including the primary care .
it is prudent to be aware of such rare side effects of antibiotics , which might need the attention of a specialist mental health professional .
hence , it is recommended that a close watch to be kept for serious psychiatric manifestation in patients receiving quinolone antibiotics .
antibiotics are the one of the most commonly used group , of drugs , in general medical and surgical practice . 
 the quinolone antibiotics can lead to a range of adverse neuropsychiatric effects with most of the reports due to ciprofloxacin and ofloxacin . here , we report an interesting and rarely described psychiatric manifestation of recurrent mania following the use of quinolone antibiotics , and briefly review the available literature .