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Paper text:
valproate is a well - established treatment in various types of seizure like absence , generalized tonic clonic ( gtc ) , myoclonic and atonic types , and also in mood disorders .
the clinical utility of this drug may be compromised by its adverse drug reaction ( adr ) such as tremor , weight gain , hair loss , and gastrointestinal disturbances , heart burn , liver dysfunction , and thrombocytopenia .
hair loss , being one of the adr with valproate having incidence of 3.5% , is diffused and non - scarring , which is related with high drug level .
however , adrs showing relation between serum levels of valproate and occurrence of hair loss are not reported .
a 26-year - old woman weighing 36 kg , suffering from gtc seizures since past six years and hypothyroidism since past 14 years , came to our therapeutic drug monitoring ( tdm ) out patient department for routine drug monitoring .
she complained of hair loss since ten months after starting valproate . during last five years
, she was receiving tablet phenytoin 100 mg thrice a day with calcium tablets along with thyroxin 50 g tablets once daily prior to valproate .
her electroencephalography ( eeg ) was normal and showed no evidence of neuronal hyper excitability ; ct scan did not reveal any significant intracranial abnormality . during the course of illness she had fluctuations in thyroid hormone levels in 2005 .
thyroid stimulating hormone levels ( > 100 iu / ml ; normal 0.3 - 0.5 iu / ml ) , reduction in total thyroxin ( 3.16 g / dl ; normal 4.5 - 12 g / dl ) , and free thyroxin was reduced ( 0.46 ng / dl ; normal 0.7 - 1.8 ng / dl ) .
the dose of thyroxin was increased to 75 g and she was stable and continued with phenytoin with regular drug monitoring . in december 2009 , she developed long term adrs of phenytoin like hypochromic , microcytic anemia with macrocytosis , and gingival hyperplasia .
phenytoin was replaced with valproate chrono 300 mg twice daily , following which her hemogram and peripheral blood smear showed normocytic picture , but three months later she complained hair loss .
she was prescribed arnicated hair oil ( arnica montana , cantharis , jaborandi , and lycopodium in gently perfumed oil base ) for local application , but no improvement was observed .
the result of trichogram revealed an increase in resting ( telogen ) and dystrophic hair at the expense of growing hair ( anagen ) , which is classical of drug- induced hair loss .
the signs of common conditions like anemia and hypothyroidism , which are often associated with diffuse hair loss , were excluded since hemogram , thyroid hormones profile , and electrolytes were normal .
subsequently , we informed the patient 's neurologist that she was probably suffering from a valproate - induced telogen effluvium and suggested its substitution with an alternative drug .
the new drug was well - tolerated and also effective in preventing seizures . in our case , the temporality between valproate intake , drug levels , and hair loss was evident , and after stopping valproate , hair loss retracted .
drug - induced hair loss is usually described as a diffuse non - scarring hair loss , which is reversible upon withdrawal of the drug .
there is a long list of drugs that on occasion have been cited as causing hair loss like sodium valproate , lithium , carbamazepine , clomiphene citrate , oral contraceptives , potassium thiocyanate , propanolol , warfarin , olanzepine , risperidone , and many antineoplastic drugs , etc .
drugs may affect hair follicles through two main mechanisms : ( i ) anagen effluvium is a prominent adverse effect of antineoplastic agents , which cause acute damage of rapidly dividing hair matrix cells .
( ii ) telogen effluvium ( precipitating the follicles into premature rest ) , which may be a consequence of a large number of other drugs like anticoagulants , interferons , and antihyperlipidemic drugs .
drug - related hair loss is not always easy to diagnose , and requires an understanding of normal hair growth and many different causal factors that are involved in it . in this patient ,
other causes of hair loss were excluded on the basis of the clinical presentation and the trichogram .
we can also suspect that the patients who develop drug - induced hair loss have predisposing factor like hypothyroidism , but her thyroid profile was normal at the time of diagnosis .
there is a possible correlation between the therapeutic dose and the serum levels of valproate and side effects , such as hair loss .
, this is consistent with high levels of valproate in blood [ table 1 ] . serum levels of valproate by therapeutic drug monitoring management of hair loss includes reassurance , hair care techniques , and if possible , drug substitution . in clinical practice ,
sometimes clinicians may be reluctant to discontinue medications in patients suffering from hair loss , if the valproate is otherwise efficacious .
if the withdrawal of offending drug is not possible , initiating a low dose and progressively increasing the dose minimizes the side effects .
recognition of cosmetically - related side effect that might result in poor compliance in some patients is necessary .
causality assessment using naranjo 's adr probability scale defined the causality as a possible ( score 7 ) ( range : 5 - 7 ) .
deficiencies of trace elements like copper , zinc , and magnesium and inhibition of metallic enzymes that are essential for hair growth and keratinization have been suggested .
awareness about this potential problem that may contribute to cosmetic concerns in the patient is a must ; in this way , the patient is warranted for better patient compliance .
sodium valproate is a well - established treatment in epilepsy and mood disorders . 
 its utility is compromised by its adverse effects such as tremor , weight gain , hair loss , and liver dysfunction . 
 hair loss may occur when drug is used in higher dose . 
 drug - induced hair loss is diffused and non - scarring , which is reversible upon withdrawal . 
 but there are no case reports showing relation between serum levels of valproate and occurrence of hair loss . 
 so we took interest in reporting this case report .