the vast increase in the number of new psychopharmacologic agents has made more therapeutic options available , but has also complicated patient treatment .
combination therapy used in psychiatric practice makes drug interactions more likely and increases the risk of adverse outcomes to the patients .
many interactions have minor clinical significance ; however , there are many potentially hazardous interactions that should always be considered
. the significance of a drug interaction can also vary between individuals , depending on factors such as co - morbidities , gender , and age . according to a recently published study
, psychiatric medications can account for up to 50% of the adverse drug reactions ( adrs ) for hospitalized patients with mental illness , many of which can be attributed to drug  drug interactions .
it has been estimated that 26% of adrs requiring hospital admissions may be due to drug  drug interactions .
haloperidol is a psychotropic drug of the butyrophenone family and is used for both chronic and short - term therapy .
parkinsonism is one of the most common extrapyramidal side effects ( eps ) of haloperidol .
there are reports on drug  drug interactions of haloperidol with neuroleptics , drugs known to prolong the qt interval , and drugs known to cause electrolyte imbalance , and the interactions are pharmacodynamic in nature .
we are reporting a case of drug interaction of haloperidol with levodopa in a parkinsonism patient .
a 60-year - old female weighing 52 kg was admitted to the hospital with the complaints of excessive drooling , involuntary movements of upper and lower limbs , slurring of speech , and difficulty in walking with stiffness in arms and legs since 12 weeks .
ten years back , she was diagnosed to have parkinsonism disease and initiated on antiparkinsonian drugs .
she was on tablet syndopa 110 mg tid and tablet trihexyphenidyl ( thp ) 1 mg tid for past 3 years .
four months ago , she had consulted a local doctor for decreased sleep and headache and was prescribed tablet haloperidol 5 mg tid .
a month latter , she visited our hospital and was admitted to the inpatient psychiatric unit with an additional diagnosis of neuroleptic - induced parkinsonism . on physical examination , she was found to have bradykinesia , lip smacking , flexed posture , and cogwheel rigidity .
findings from her routine blood work including complete blood cell count with differential and comprehensive metabolic profile were within normal limits .
based on literature search and detailed review of the patient medical history , haloperidol was suspected to be the causative agent for current episode in this patient and was replaced with tablet risperidone 1 mg bd .
however , she continued to receive syndopa ( 110 bd ) and thp ( 2 mg in the morning ) during the remaining 11 days of her hospital stay .
three days later , she was discharged with tablet syndopa 110 bd , tablet thp 2 mg one in the morning and one in the noon , and tablet clonazepam 0.5 mg hs , and advice for review after 2 weeks .
a drug interaction occurs when the toxicity or effectiveness of a drug is altered by the concurrent administration of another drug .
a pharmacokinetic drug interaction occurs when a drug alters the absorption , distribution , metabolism , or excretion of another drug .
pharmacodynamic interactions occur when two drugs act on interrelated receptor sites , resulting in either additive or antagonistic effect .
drug interactions have been documented to occur with many agents commonly used in conjunction with antipsychotics such as anticholinergics , anticonvulsants , antidepressants , anxiolytics , and lithium .
it is widely recognized that neuroleptic drugs can induce a state of parkinsonism , a major adverse reaction attributed to antagonism at striatal dopamine receptors .
the temporal relationship between starting of haloperidol and progression of the patient 's parkinsonian signs confirms that this clinical observation is very likely to be due to haloperidol .
one explanation of our finding is the possibility of drug  drug interaction of haloperidol and levodopa .
haloperidol reduces the efficacy of levodopa in parkinson 's disease by blockade of dopamine receptors in the corpus striatum .
the result may be worsening motor function , a relapse of psychosis , or a combination of both .
positron emission tomography ( pet ) studies have indicated that the therapeutic effects of antipsychotics are achieved at a blockade of 60 - 70% of dopamine receptors , and antipsychotic - induced parkinsonism ( aip ) was observed at d2 occupancy of 34 - 80%
. a greater affinity of conventional antipsychotics for dopamine d2 receptors may account for their increased risk of aip . several studies have reported that between 26% and 67% of patients using conventional antipsychotics develop aip .
the interval between initiation of antipsychotics and onset of aip is highly variable , ranging from a few days to several months . in our case ,
although no rechallenge was attempted , the symptoms were improved after 11 days of cessation of haloperidol , which is suggestive of possible association between haloperidol and the current episode of patient condition . besides that , elderly people are more prone to develop adverse drug interactions because of their age - related changes in the pharmacokinetic and pharmacodynamic parameters .
it is well documented that younger people tend to metabolize the drug faster than older people , and men faster than women . according to different studies ,
most likely , a combination of these factors , i.e. dopamine blocking , drug interaction , age , high dose of the drug , and gender , may have given rise to this episode of parkinsonism .
the probability of a causal relationship between a potential drug interaction and the event was  possible ,  as assessed by drug interaction probability scale ( dips ) . in practice
, only a few of the possible drug interactions may be clinically relevant ; the practitioner must still consider the critical factors associated with drug  drug interactions .
such factors include the potency and concentration of the drugs involved , the therapeutic index balanced between efficacy and toxicity , the presence of active metabolites , and the extent of the metabolism of the substrate drug .
it is imperative that all healthcare professionals working with older adult population should take a comprehensive medication history and do careful monitoring for identification , management , and prevention of negative clinical consequences .
the influence of aip on the quality of life of elderly patients should be evaluated . with the increase in the number and types of medications being prescribed for or used by patients , it is important to look at all medications , including over - the - counter ones .
 drug interactions are known to play a significant role in the incidence of adverse drug reactions ( adrs ) both in the community and in hospitals . 
 both the newer atypical antipsychotics and their more traditional counterparts are subject to drug  drug interactions amongst themselves , with other psychotropics , and with the agents used in the treatment of various physical ailments . 
 the most common interactions encountered in clinical practice are pharmacodynamic in nature . 
 it is well established that antipsychotic drugs reduce the efficacy of levodopa in parkinson 's disease by blockade of dopamine receptors in the corpus striatum . 
 the case reported here illustrates a common pharmacodynamic drug interaction of haloperidol with levodopa in a 60-year - old female patient . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSION