Clozapine: the correlation between clinical improvement and laboratory parameters
Abstract
English: In this study, fifteen Black patients suffering from
acute schizophrenia were treated with clozapine for
a period of 40 days in order to ascertain whether
certain laboratory parameters could be utilized to
give an indication of the clinical efficacy of clozapine
treatment in these patients.
S.l.l Therapeutic efficacy
Utilizing the B.P.R.S. and F.C. rating scale as
indication of the clinical improvement of the
patients, it was found that significant clinical
improvement occurred upto day 30 whereafter clinical
improvement was only slight. Clozapine
was well tolerated by all the patients while more
than half the patients (53,3%) were fit for unmndhional
discharge on completion .of the study.
On completion of the study the working capacity
of the majority (80%) was satisfactory.
5.1.2 Side effects
The most common side effects encountered were daytime
sedation which was especially prominent during
the early stages of the study and hypersalivation which occurred with equal frequency throughout the
study period. Other side effects encountered in
descending order of frequency were nausea and
vomiting, dizziness, headache, disturbance of visual accomodation, constipation and diarrhoea, disturbed
sleep, sweating, inhibition of micturition, and
collapse.
5.1.3 Blood pressure and pulse rate
Clozapine had no significant' prolongated effect
on blood pressure while a significant and sustained
rise in pulse rate during the treatment period was
noted. It is suggested that this rise in pulse
rate could be utilized as a convenient clinical aid
in checking patient compliance in patients being
treated with clozapine.
5.1.4 Serum concentration of clozapine, clozapine plus
metabolites, and metabolites only.
5.1.4.1 No correlation was found between serum
levels of clozapine, clozapine plus its
metabolites, or its metabolites only and
clinical improvement.
5.1.4.2 It was found that on treatment day 5 steady
state serum levels of clozapine and of
clozapine plus it metabolites had been
reached.
5.1.4.3 No auto-induction of the metabolism of
clozapine appeared to occur during the
treatment period.
5.1.4.4 No accumulation of clozapine or its metabolites
appeared to occur during the treatment
period.
5.1.4.5 It can be concluded that a certain period
of exposure to a more or less constant
serum level of clozapine and/or its metabolites
is necessary to effect clinical
improvement.
5.1.4.6 A significant correlation was found between
the lying pulse rate and serum levels of
clozapine plus its metabolites. The lying
pulse rate can thus offer a reasonable indication
of the expected serum levels of
clozapine plus its metabolites.
5.1.5 Prolactin serum levels
No rise in serum prolactin levels occurred in these
patients after institution of treatment with clozapine.
Therefore no correlation between clinical
improvement and prolactin serum levels could be
ascertained.
5.1.6 5-hydroxytryptamine-induced platelet aggregation
No enhancement of 5-HT-induced platelet aggregation
could be determined in these patients undergoing
treatment with clozapine. Therefore no correlation
could be established between clinical improvement
and enhancement of 5-HT-induced platelet aggregation.
5.1.7 Plasma cholinesterase and red blood cell ace~-
cholinesterase activitX'
Both the plasma cholinesterase and red blood cell acetylcholinesterase activity fell within the
normal range prior to the institution of treatment
with clozapine. These parameters can
therefore not be used as diagnostic aids in the
diagnosis of schizophrenia. The activity of
both parameters also fell within the normal range
on conclusion of the study. It would thus
appear that treatment with clozapine did not
significantly affect these·.parameters. Afrikaans: Tydens hierdie studie is vyftien Swart pasiënte wat gely
het aan akute skisofrenie behandel met klosapien vir 'n
periode van 40 dae om vas te stelof sekere laboratorium
parameters gebruik kon word om 'n aanduiding te gee van
die kliniese bruikbaarheid van klosapien behandeling by
hierdie pasiënte.
5.2.1 Terapeutiese bruikbaarheid
Deur gebruik te maak van die Verkorte Psigiatriese
Beoordelingskaal (B.P.R.S.) en die F.C. beoordelingsskaal
om die kliniese verbetering van die pasiënte
te beoordeel, is gevind dat betekenisvolle kliniese
verbetering plaasgevind het tot op dag 30 waarna
slegs 'n geringe verbetering plaasgevind het.
Klosapien is goed verdra deur al die pasiënte terwyl
meer as die helfte van die pasiënte (53,3%) geskik gevind is vir onvoorwaardelike ontslag ten voltooiing
van die studie. Na voltooiing van die
studie was die werksvermoë van die meeste pasiënte
(80%) gevind om bevredigend te wees.
5.2.2 Newe-effekte
Die mees algemene newe-effekte wat voorgekom het
was sedasie (wat veral voorgekom het tydens die
eerste deel van die studie) en hipersalivasie die
voorkoms waarvan dieselfde gebly het gedurende die
hele studie tydperk. Ander newe-effekte wat voorgekom
het in volgorde van frekwensie (algemeen tot
seldsaam) is naarheid en braking, duiseligheid,
hoofpyn, versteuring van visuele akkommodasie, hardlywigheid
en diaree, verstoorde slaap, sweet, inhibisie
van urinering en kollaps.
5.2.3 Bloeddruk en polsspoed
Klosapien het geen betekenisvolle uitwerking op
bloeddruk gehad nie terwyl 'n betekenisvolle en
volgehoue styging in polsspoed gedurende die behandelingstydperk
waargeneem is. Dit word voorgestel
dat hierdie verhoging in polsspoed gebruik
kan word as 'n kliniese hulpmiddelom vas te stel
of die pasiënt wel die medikasie neem in die geval
van pasiënte wat met klosapien behandel word.
5.2.4 Serumkonsentrasie van klosapien, klosapien plus
metaboliete en metaboliete alleen.
5.2.4.1 Geen korrelasie is gevind tussen serumvlakke van klosapien, klosapien plus metaboliete
of die metaboliete alleen en kliniese
verbetering nie.
5.2.4.2 Daar is gevind dat gelykvlak van klosapien
en klosapien plus sy metaboliete reeds op
dag 5 voorgekom het.
5.2.4.3 Geen outoinduksie van die metabolisme van
klosapien blyk om voor te kom tydens die
behandelings tydperk nie.
5.2.4.4 Geen akkumulasie van klosapien of sy metaboliete
kom voor tydens die behandelingstydperk
nie.
5.2.4.5 Die afleiding kan gemaak word dat 'n sekere
tydperk van blootstelling aan 'n min of
meer konstante serumvlak van klosapien en/of
sy metaboliete.nodig is om kliniese verbetering
teweeg te bring.
5.2.4.6 'n Betekenisvolle korrelasie is gevind tussen
die liggende polsspoed en die serumvlakke van klosapien plus sy metaboliete. Die
liggende polsspoed kan dus 'n aanduiding
gee van die verwagte serumvlakke van klosapien
plus sy metaboliete.
5.2.5 Prolaktien serumvlakke
Geen verhoging in prolaktien serumvlakke het voorgekom
nadat die pasiënte met klosapien behandel is nie,
derhalwe kon geen korrelasie tussen kliniese verbetering
en prolaktien serumvlakke aangetoon word nie.
S.2r6 5-hidroksitriptamiengeïnduseerde plaatjiekleefbaarheid
Geen versterking van 5-HT-geïnduseerde plaatjiekleefbaarheid
kon vasgestel word in hierdie
pasiënte wat met klosapien behandel is nie.
Derhalwe kon geen korrelasie vasgestel word tussen
kliniese verbetering en versterkte 5-HT-geïnduseerde
plaatjiekleefbaarheid nie.
5.2.7 Plasmacholienesterase en rooibloedselasetielcholienesterase
aktiwiteit
Beide die plasmacholienesterase en rooibloedselasetielcholienesterase
aktiwiteit was binne die
normale perke voordat 'n aanvang geneem is met
klosapienbehandeling. Hierdie parameters kan dus
nie as diagnostiese hulpmiddels gebruik word by die
diagnose van skisofrenien~.Die aktiwiteit van
beide parameters het ook binne die normale perke
geval na voltooiing van die studie. Dit blyk
dus dat behandeling met klosapien nie hierdie parameters
betekenisvol beïnvloed het nie.