Olanzapine is a 2nd coevals antipsychotic medicine that is widely used in patients with schizophrenic disorder, schizoaffective, bipolar upset and treatment-resistant depression. The drug is besides used off-label in other psychotic upsets, behavioural perturbations in dementedness, kids and striplings, impulse control upsets and marginal personality upset. ( 1, 2 ) Consequences of the randomized-controlled and matter-of-fact tests strongly back up its efficaciousness and effectivity. Consequences of CATIE survey strengthened its usage in patients with schizophrenic disorder. Olanzapine proved its efficaciousness in all stages of CATIE test. Olanzapine and Clozaril had the greatest liability to bring on side effects. ( 3, 4 ) Olanzapine has a well-known leaning to bring on metabolic side effects like: clinically important weight addition, hyperglycaemia, lipid abnormalcies which wholly can take to metabolic syndrome. We will present a patient with schizophrenic disorder, who has been treated with olanzapine and showed terrible hypertriglyceridemia after medicine induction and which resolved after its surcease and medicine alteration to aripiprazole. Here, we will demo the alterations in degrees of triglyceride ( TG ) , glucose, weight, cholesterin, waist perimeter, blood force per unit area before and at 1 hebdomad and 2 hebdomads after the surcease of olanzapine.
Case Raport
27-year-old adult male, individual, with secondary instruction, employed as printing machine operator, populating with his female parent, with no important medical history, was diagnosed with schizophrenic disorder paranoiac type harmonizing make DSM-IV-TR standards. He was put on antipsychotic medicine ( risperidone ) . The dose was bit by bit increased to 3 milligram of that medicine given in the eventide. The medicine was good tolerated. During hospitalization patient ‘s blood was drawn for research lab trials. Table 1 describes research lab findings before intervention with risperidone was initiated ( clip point – t0 ) . No important divergences from the normal scope was seen apart from mildly increased entire cholesterin ( CHOL ) and triglycerides ( TG ) degree. Treatment with risperidone resulted in about complete diagnostic and functional recovery. Patient ‘s psychic province has well improved, the patient regained disease penetration and positive symptoms have subsided. The patient showed marks of blunted affect and complied with amotivation, anhedonia and deficiency of energy. One month after admittance the patient was discharged from the infirmary. Come back to work and was working usually in his usual functions.
Subsequently the patient was consulted in the out-patient section of our infirmary. Two months after being discharged from psychiatric unit the patient decided to halt intervention without audience with his head-shrinker. One month after risperidone discontinuance psychotic symptoms recurred. After psychiatric audience risperidone was started once more. The dose was bit by bit increased to 5 milligrams a twenty-four hours. The medicine was stopped after six hebdomads class due to miss of efficaciousness and extrapyramidal side effects ( akathisia ) and continuity of depressive symptoms. Consulting head-shrinker decided to get down intervention with olanzapine. Table 1 summarizes the consequences of laboratory trials before olanzapine therapy was started ( clip point – t1 ) . Olanzapine dose was easy increased to 15 milligrams given at bedtime. Psychotic symptoms resolved in less than a month of olanzapine therapy, nevertheless the patient was kicking of sedation during the twenty-four hours, deficiency of energy, sickness and concentration troubles and episodes of abdominal hurting. No apparent pathology was seen on physical scrutiny. The being of the above symptoms and the demand to supervise side effects of major tranquilizers harmonizing to the Polish guidelines made the head-shrinker to order research lab trials. The consequences are summarized in table 1 in the column described as clip point – t2. Apparent hypertriglyceridemia was observed with triglycerides level above 700 mg/dl and 900 mg/dl in the subsequent analysis ( t3 ) . Entire cholesterin was besides increased to 390 mg/dl. Transaminases activity was 6-7 times above the upper bound of the normal scope and hematoidin degree was about 3 mg/dl.
Other common causes of hypertriglyceridemia were excluded on the footing of extra research lab trials and past medical history. Olanzapine-induced assorted dyslipidemia with a predomination of hypertriglyceridemia was diagnosed. Antipsychotic medicine was changed. Olanzapine was bit by bit withdrawn while aripiprazole therapy was initiated and the dose was easy increased to make 30 mg a twenty-four hours given in the forenoon. Olanzapine discontinuance and intervention with aripiprazole resulted in lessening of triglyceride degrees about to normal scope. The patient was advised to follow a Mediterranean diet and have a regular monitoring of the lipid profile.
Table 1 summarizes laboratory trial consequences 1week ( t4 ) and 2 hebdomads ( t5 ) after olanzapine discontinuance. No important divergences from the mention scope of metabolic profile and liver map trials were seen. CHOL and TG were somewhat increased, 226.4 mg/dl and 156.2 mg/dl severally. Severe hypertriglyceridemia was revealed after 12 hebdomads of olanzapine therapy and it subsided 1 hebdomad after olanzapine discontinuance and 3 hebdomads after aripiprazole debut.
Discussion
Olanzapine is a 2nd coevals antipsychotic that is structurally similar to clozapine. Both medicines portion to same extent their side-effects profile. Olanzapine therapy can take to a broad scope of metabolic side effects, like weight addition ( 2, 5 ) , glucose dysregulation ( 6, 7 ) , diabetes mellitus ( 8, 9 ) , hyperglycemic non-ketonic coma ( 10, 11 ) and diabetic diabetic acidosis ( 12, 13 ) . Apart from these metabolic adverse effects, olanzapine can bring on dangerous conditions, like acute hepatocellular-cholestatic liver hurt ( 14 ) every bit good as venous thromboembolism ( 15 ) and acute pancreatitis. ( 16, 17 ) Olanzapine was besides found to be one of the four major tranquilizers bring oning liver harm most often in the Polish survey. ( 18 ) Hypertriglyceridemia was besides observed in the class of olanzapine therapy. ( 19, 20 ) MHRA Public Assessment Report for olanzapine summarizes the frequence of side effects. ( 21 ) Harmonizing to that papers the most frequent metabolic side effects of olanzapine include: weight addition ( & A ; gt ; 10 % ) , hypertriglyceridemia and hypercholesteremia ( 1-10 % ) , hyperglycaemia ( 1-10 % ) , glucosuria ( 1-10 % ) , transient, symptomless lifts of transaminases ( ALT, AST ) , particularly in early intervention ( 1-10 % ) . Pancreatitis, diabetic coma with diabetic acidosis, venous thromboembolism are regarded as potentially dangerous but comparatively rare conditions seen in less than 1 % of instances. ( 21 )
Osser et Al. observed metabolic and lipid profile alterations during 12-week olanzapine therapy in 24 patients ( chiefly work forces ) with schizophrenic disorder. ( 22 ) Mean olanzapine dosage used was 13.8 milligram. The writers observed a average addition of organic structure weight ( 5.4 kilogram ) , with the attach toing average fasting TG lift of 60 mg/dL to 222 ± 135 mg/dL ( average ± SD ) . The association between weight addition and TG lift was so strong that after commanding for weight, analysis of covariance showed no independent addition in triglycerides. Yamamoto et Al. described a instance of an adolescent male patient who developed hypertriglyceridemia during olanzapine therapy and found a relationship between leaning for triglycerides lift, weight addition and decreased lipoprotein lipase ( LPL ) activity. ( 23 ) The writers suggested that weight addition and hypertriglyceridemia induced by olanzapine were due to diminish in LPL activity.
Different information was obtained by other writers. Adachi et Al. described a instance of 40-year-old male patient referred due to terrible hypertriglyceridemia ( TG: 1,598 mg/dl ) induced by olanzapine. ( 24 ) TG lift in that patient was non connected with organic structure weight addition nor fasting glucose degree addition. To understand which TG-rich lipoprotein is of import for olanzapine-induced hypertriglyceridemia, the writers measured each lipoprotein fraction by the anion-exchange high-performance liquid chromatography. They found that very-low denseness lipoprotein ( VLDL-C ) was the most of import lipoprotein for olanzapine-induced hypertriglyceridemia. VLDL degree was unusually high during olanzapine therapy and it quickly decreased after olanzapine surcease. The degree of VLDL about paralleled decreasing TG degree. Adachi et Al. found besides a positive correlativity between olanzapine-induced TG lift and high-sensitivity C-reactive protein ( hs-CRP ) . Cessation of olanzapine lead to diminish of hs-CRP and addition of adiponectine. Unlike Osser et al. , these writers did non detect important LPL activity alterations after discontinuance of olanzapine. VLDL is a TG rich lipoprotein. It is composed of 55 % TG, 20 % of cholesterin and 15 % of protein. VLDL is produced in the liver and conveyances lipoids to musculuss and fat tissue. ( 25, 26 ) Adachi et Al. speculated that olanzapine might bring on redness and cut down adiponectin, taking to activation of hormone-sensitive lipase which hydrolyzes TG to liberate fatty acids ( FFA ) . Increased go arounding FFA may come in the liver, ensuing in hepatic overrun of VLDL and hepatic steatosis.
The patient described in the present instance study developed a terrible lift of TG which was apparent 12 hebdomads after induction of olanzapine therapy. Secondary causes of hypertriglyceridemia, which are summarized in table 2, were besides ruled out. Primary and familial causes of hypertriglyceridemia could be excluded on the footing of household history and deficiency of important divergences from mention scope observed before olanzapine intervention was introduced. Since all other primary and secondary causes were excluded, the metabolic abnormalcies could merely be attributed to olanzapine. Temporal relationship besides points to olanzapine as a likely cause of metabolic alterations described above.
The described patient did non see important organic structure weight nor fasting glucose flat addition during olanzapine therapy. Hypertriglyceridemia was correlated with marks of the liver harm ( aminotransferase lift ) which resolved after olanzapine discontinuance and induction of therapy with aripiprazol. The latter medicine was chosen because lower leaning to bring on metabolic and hepatic side effects. Aripiprazole has good overall safety profile. Keck et Al. conducted a 100 hebdomad bipolar care intervention survey utilizing aripiprazole in comparing with placebo. ( 27 ) The following metabolic or cardiovascular side effects were seen in that survey: high blood pressure in 7.8 % ( placebo 3.6 % ) and weight addition in 6.5 % ( placebo 0 % ) of patients, while aripiprazole had no consequence on QTc interval of the ECG, entire cholesterin, LDL or HDL cholesterin, triglycerides, or glucose degrees. Long-run test conducted in 555 patients with schizophrenic disorder revealed that weight alterations and weight related quality of life were better with aripiprazole, compared to olanzapine, quetiapine and risperidone. ( 28 ) However, there are besides rare instance studies depicting hypertriglyceridemia induced by aripiprazol. ( 29 ) That is why despite its good overall safety profile, clinical monitoring of metabolic side effects is still recommended in patients treated with aripiprazole. The patient described in our study had his antipsychotic intervention changed from olanzapine into aripiprazole and this led to diagnostic and functional remittal of schizophrenic disorder symptoms every bit good as standardization of metabolic alterations and declaration of liver harm induced before by olanzapine.
Aripiprazole was compared with placebo as the add-on antipsychotic in olanzapine-treated stable schizophrenic disorder patients with fleshiness. ( 30 ) During the 4 hebdomads of aripiprazole intervention ( 15 mg/d ) , there were important lessenings in weight and organic structure mass index compared with placebo. The writers did non detect important differences in cholesterin degree between groups. However, entire serum triglycerides decreased significantly during the aripiprazole intervention stage. There was a lessening in C-reactive protein comparing aripiprazole intervention to placebo, although it did non make statistical significance degree.
To writers best cognition this is the first instance study of hypertriglyceridemia and liver harm induced by olanzapine which were successfully treated with medicine discontinuance and alteration to aripiprazole with a good clinical result and side effects alleviation.
Decisions
Olanzapine may bring on hypertriglyceridemia and liver harm in susceptible persons.
Aripiprazole may be used with success alternatively of olanzapine in instances of hypertriglyceridemia.
Patients ‘ lipid profile should be checked during olanzapine therapy to avoid serious complications.
Recognition
This paper was supported by a grant N N402 243435 from the Polish Ministry of Science and Higher Education.
Table 1. Changes of metabolic parametric quantities observed during the class of olanzapine intervention
Time point
Variable
T0
T1
T2
T3
T4
T5
Conversion factor
SI Unit of measurements
Treatment
Before risperidone
risperidone
olanzapine
olanzapine
aripiprazole
aripiprazole
Triglycerides [ mg/dl ]
154
156.2
761.3
936.1
166.8
191.7
0.0113
mmol/l
Entire Cholesterol [ mg/dl ]
212.5
226.4
390
300.7
243.5
249.7
0.0259
mmol/l
HDL Cholesterol [ mg/dl ]
44.1
66.2
38.4
19.7
41.7
43.3
0.0259
mmol/l
LDL Cholesterol [ mg/dl ]
137.6
108.9
–
–
168.4
168.0
0.0259
mmol/l
Glucose [ mg/dl ]
91.9
88.7
104.7
85.9
92.4
94.9
0.0555
mmol/l
ALT [ U/l ]
33.0
–
237
248.0
48.0
–
1
U/l
AST [ U/l ]
36.0
–
307
329.0
28.0
–
1
U/l
Bilirubin [ mg/dl ]
0.8
–
2.4
2.7
0.6
–
17.1
µmol/L
Weight [ kg ]
79.7
76.5
76.5
75.1
–
78.4
1
kilogram
BMI [ kg/m2 ]
24.06
23.97
23.1
22.7
–
23.7
1
kg/m2
Waist perimeter [ centimeter ]
97
95
95
93
–
96
0.01
m
Systolic BP [ mmHg ]
137
133
136
134
–
128
7.5006-10?3
Pa
Diastolic BP [ mmHg ]
87
85
88
82
–
82
7.5006-10?3
Pa
T0 – Before risperidone induction ; T1 – risperidone ( 10 hebdomads ) 4 mg/d ; T2 – olanzapine ( 12 hebdomads ) 15 mg/d ; T3 – olanzapine ( 13 hebdomads ) 20 mg/d ; T4 – 1 hebdomad after olanzapine discontinuance ; aripiprazole ( 3 hebdomads ) ; 30 mg/d ; T5 – 2 hebdomads after olanzapine discontinuance, aripiprazole ( 4 hebdomads ) ; 30 mg/d ; ALT – alanine transaminase ; AST – aspartate transaminase
Table 2. Secondary causes of hypertriglyceridemia which were ruled out in the described patient on the footing of medical history and research lab findings.
Type of cause
Cause
Metabolic causes
Diabetess mellitus type 1 and 2
Fleshiness
Hypothyroidism
Nephrotic syndrome and end-stage nephritic disease
Medicines
High-dose thiazide water pills
High-dose beta-adrenergic blocking agents, excepting those with intrinsic adrenergic activity
Unopposed unwritten estrogen replacing therapy
Oral preventives with high estrogen content
Estrogen antagonist
Glucocorticoids
Oral isotretinoin
Antiretroviral therapy
Other causes
Excessive intoxicant consumption
High-carbohydrate diets
Acute pancreatitis
Pregnancy
