Carbamazepine and Serum Sodium Levels

Abstract

Serum sodium levels of 674 epileptic patients were tabulated according to the following categories: less than 135 mmol/L, hyponatremia (28 patients); 135-145 mmol/L, normonatremia (530 patients); greater than 145 mmol/L, hypernatremia (116 patients). One hundred one patients were treated with antiepileptics without carbamazepine (CBZ), 113 with CBZ monotherapy, and 460 with CBZ plus other antiepileptic drugs. Twenty-three patients could be followed up after the first detection of a serum sodium level of less than 135 mg/L. Ten patients were consistently hyponatremic (greater than 50% of the follow-up measurements were less than 135 mg/L), whereas the remaining 13 were occasionally hyponatremic. The following facts could be derived from the study: (1) The hyponatremic group was significantly older compared with the other groups. (2) In patients not treated with CBZ, no hyponatremia was seen. Only two patients on CBZ monotherapy showed hyponatremia. (3) The combination of CBZ, valproic acid, especially in high dosages, and barbiturates seemed to lead to hyponatremia. (4) The excretion of antidiuretic hormone, measured in 12 patients, was subnormal (less than 25 ng/24 h) in seven hyponatremic patients and in three normonatremic patients and normal (25-250 ng/24 h) in two other normonatremic patients. (5) Cyclic AMP, measured in five hyponatremic patients, was normal. (6) In all patients the hyponatremia was slight and did not cause any clinical symptoms. Special treatment was not required.

Carbamazepine-Associated Hyponatremia

“…Mu ch of th e difficulty conce rn ing th e iden t ifica t ion of C Bl-ind uce d hyp on atremia involves th e high percent a ge of asymp tomati c individ uals with hypon a tremi a. In this case report , only hal f t he pati e n ts were sym p to ma tic, a nd in o t he r case rep or ts by O 'Ha re e t a l. (30) and Kal ff and cowo r ke rs (22) eve n th e most seve re ly affected hypo natrem ic pa ti en ts we re asymptom atic. An add it iona l com plica t ion in th e clinical d ia gn osis of C Bl-ind uce d hypo na t re m ia occurs from th e overla p of sym pto ms rel ating to C Bl in to xica t ion .…”

“…Nu me ro us ca se s, mo stly associa te d with neurological di sorders, d escribi ng CBlinduced hyponatremia have been report ed in th e lit erature over th e past 20 years (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Again no conclusions ca n be drawn du e to th e sm a ll sa m ple size; howeve r, some ge ne ra liza t ions ca n be described.…”

“…For exam ple, stu dies by Kal ff a nd cowork ers (22) a nd Lahr (23) identify age as a n import ant risk fact o r; wh ereas num e ro us studi es (24-31 ) do not d em on strat e a co r re la t ion bet ween age a nd C Bl-ind uce d hyponat re m ia. Simi larl y, C Bl se rum levels have been associa te d wit h hypo na t re m ia in st ud ies by H enry and cowo r ke rs (27), La hr (23), Ka lff an d colleagues (22) , O ' Hare a nd associat es (30), while H eli n a nd coworke rs (25) , joffe and associat es (29), and Vieweg a nd cowor kers (32) have no t obse rve d a re lat ions hi p be tween C Bl serum levels and hypon at remi a.…”

“…Frah m and colleag ues (35), Kimu ra a nd associa tes (36), and Asht on a nd cowo r kers ( 10) pr esent evide nce cons iste n t with a CBZ-induced hypersecr etion of ADH; howeve r, both Frahm a nd coa u t ho rs (35) a nd Kimura and colle ag ues (36) use a bioassay, t he hydrat ed rat , whi ch m easures ac t ivity and not conce ntra t ion of ADH. Co nversely, Ka lff and ass ocia tes (22) , G old a nd cowor ke rs (37) , S te phe ns a nd coa u t hors (38) , Meinders a nd colleagues (39) a nd Thom as a nd associa tes (40) do not su pport t he findin g th at CBZ incr ea ses ADH sec re tio n. Furtherm or e, th ese st udies e m ploy radioimmunoa ssay (RIA) whi ch a t te m p ts to dir ectl y det ermine th e co nce n t rat ion of AD H , and consequ ent ly, t hese st ud ies con tain a more re liab le assa y for ADH as com pared with a bioassay. M einders a nd associa tes (39) conclude in th eir st udy th at C BZ sensitizes o r ac ts direct ly o n th e renal tubules t o produce a positive synergis tic effec t with ADH .…”

“…Unfortunat ely, t he a n t id iu re tic effect of C BZ ca n signifi cantly co m plica te th e effec t ive ne ss of C BZ for th e treatm ent of psychiatric disord er s by producin g hypon atrem ia. Nu merous case re po rts (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), studi es (23)(24)(25)(26)(27)(28)(29)(30)(31)(32), an d two reviews (33,34) have clearly document ed th e pr obl e m ; however, litt le co nse ns us prevail s towards underst anding eit her th e mech an ism or pr edisposing ca uses for CBZ-induced hyp on atremia.…”