Chiaramente, ogni formato ha i propri vantaggi e svantaggi comprare amoxil senza ricetta per effettuare un acquisto, non è necessario fornire la prescrizione medica.

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Comparative efficacy of haloperidol and olanzapine in
patients of schizophrenia: a 6 month follow up trial
Romika Dhar, BS Chavan, Ajeet Sidana
Abstract : P
resent study was carried out to compare the efficacy f olanzapine and haloperidol in patients of schizophrenia. A prospectiv randomized, open label studycarried out on patients attending the outpatient clinic or those admitted to inpatientservices. 40 cases of schizophrenia diagnosed as per ICD-10 were randomized toolanzapine and haloperidol group and were assessed at 3 months andafter 6 months of treatment using scales PANSS and ESRS. the study showed thatboth the drugs were equally efficacious in improving the psychopathology andhaloperidol led to increase in extrapyramidal side effects. Both olanzapine andhaloperidol are equally effective in causing clinical ment . In comparison,both the drugs do not have much difference in the cost of treatment. Keywords : E
fficacy, Haloperidol, Olanzapine, Schizophrenia JMHHB 2010; 15(1) : 31-39 only became available in the middle of the 20th Schizophr enia is a s evere and disabling ce nt ur y. 4 Nume ro us landma rk s tudi es 5-7 psychiatric disorder with devastating effects on demonstrated clearly that chlorpromazine, the both its patients and their families. It extracts a prototypic antipsychotic, was more effective than huge economic cost from the society. its usual non-pharmacologic treatment (eg, placebo, onset is in late adolescence or early adulthood, psychotherapy) in alleviating the acute symptoms and the illness generally follows a recurrent and of schizophrenia and preventing their recurrence.
chronic course. Evidence from epidemiological Initially chlorpromazine was termed a neuroleptic research indicates that schizophrenia occurs in drug to describe its effect of psychomotor all populations with prevalence in the range of immobilization. Haloperidol belonging to the 1.4 to 4.6 per 1000 and incidence rates in the chemical class of butyrophenones was developed range of 0.16-0.42 per 1000 population.1 The in the late 1950s for use in the field of anaesthesia lifetime prevalence of suicide is about 10% in and was initially used to prevent surgical shock.
patients with schizophrenia. According to the Researc h subsequent ly demonstra ted its Global Burden of Disease Study, schizophrenia beneficial effect on hallucinations,delusions, causes a high degree of disability, which accounts aggressiveness, impulsiveness and states of for 1.1% of the total Disability Adjusted Life Years excite ment .8-10 Thes e f indings le d t o t he (DALYs) and 2.8% of Years Lived with Disability.
introduction of haloperidol as an antipsychotic.
In the World Health Report 2001, schizophrenia Hailed as a breakthrough,it was considered to is listed as the 8th leading cause of DALYs be the most potent antipsychotic known, effective worldwide in the age group 15-44 years.2 Despite for a wide range of psychotic disorders and in schizophrenia 's longs tanding afflicti on of addition, appeared to keep side effects to a mankind3, effective treatment for this disorder minimum.10 Since its introduction, clinical Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia experience has suggested that haloperidol is was taken and study was approved by the ethical indeed an effective antipsychotic, particularly committee of the institute.
beneficial for those who are experiencing acute The sample consisted of 40 patients with hallucinations and delusions. after almost half a the diagnosis of Schizophrenia according to century, experience with conventional anti- ICD-10.11 20 patients each were assigned to psychotic drugs has revealed their substantial haloperidol and olanzapine group based on random table.
The introduction of clozapine treatment in Inclusion Criteria were patients in the age the United States in 1990 opened the era of group of 18 to 65 years, fulfilling criteria for "atypical" antipsychotic drugs which were Schizophrenia as per ICD 10, with IQ in normal developed with the aim to be efficacious in treatment without carrying the burden of adverse Exclusion Criteria were patients with co- extrapyramidal sideeffects which were an morbid substance related disorders except impor tant dete rmi nant of tre atment no n- nicotine, patients who fulfilled the criteria for adherence. The atypical or second generation Treatment Resistant Schizophrenia(TRS), which was defined as: antipsychotics in their lower affinity for D2receptors and relatively greater affinities for other At least two prior drug trials of at least neuroreceptors, including those for serotonin 4-6 weeks duration at 400-600 mg of and norepinephrine and in their ability to Chlorpromazine (or equivalent) without modulate glutamate receptor mediated functions significant clinical improvement.
b) Persistent psychotic symptoms which was defined as a score of > 45 on 18 di splay ing na no molar aff inity at D1–D4, item scale of BPRS and score of >4 serotonergic (5-HT2,3,6), muscarinic (subtypes (moderate) on at least two items of 1–5), adrenergic (Ü 1), and histaminergic(H1) positive symptoms of BPRS.
binding sites. There is extensive western Patients with past history of poor response to literature over this issue but studies in Indian olanzapine or haloperidol, with pre-existing settings have been very few with little emphasis diabetes mellitus, chronic medical illness, on comparability of efficacy between these two neurological disorders-head injury, tumours, different classes of antipsychotics.
movement disorder, who were pregnant and Hence the study was planned with the aim to lactating, who were unwilling to participate in compare the efficacy of olanzapine versus haloperidol over a period of six months.
hypersensitivity reaction due to haloperidol orolanzapine in the past.
MATERIAL AND METHODS
Patients were inducted from those attending the longitudinal study with an intent to treat outpatient clinic or those admitted to the analysis. The drugs of standard pharmaceutical inpat ie nt ser vi ces of the Depart me nt of companies approved by the drug committee of Psychiatry of the Government Medical College GMCH were prescribed.
and Hospital (GMCH), Chandigarh. The informed Patients who were drug naïve or who had consent from patient and close family member not been on antipsychotics in last 2 weeks were Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia started on either on olanzapine or haloperidol variables namely age, sex, marital status, as per randomization. Efforts were made to keep education, income and locality except that more the dosages of medications in the therapeutic patients in the olanzapine group came from range, that is, 5-20 mg of haloperidol and 5-20 nuclear families(85% v/s 50% ). In both the mg of olanzapine and the treating doctor was groups the maximum patients were in the age requested to keep the same therapeutic dosage group of 26-35 years. Male and females were for atleast 6 weeks and in case there was no equally distributed. W ith regards to duration of satisfactory response at the end of 6 weeks.
illness, in both the groups almost 60% of the the treating doctor was at liberty to increase patients il ness was of duration 1-5 years, mean the dose as needed and it was documented.
2.29 years and there was no statistically Though the trial consisted of 6 months of open significant difference between the two groups label ther apy, patients who di d not show with regards to duration of illness.(p value 0.229) adequate response after 3 months, that is atleast Olanzapine was used in the range of 5-30 mg , mean dose of 18.5 mg and haloperidol was used in the range of 5-15 mg , mean dose of sy mpto m sc ale fo r sc hi zo phre ni a) wer e 11.275 mg. Comparison of use of concomitant excluded from the study and started on other drugs is given in Table 1 Concominant medica tions like benzo- Use of concomitant drugs
Olanz apine
Haloper idol
concomit ant
N=20 N(% )
N=20 N (% )
counteracting extrapyramidal side effects waspermitted wherever required and were recorded in both the groups.
Benzodiazepines 4 ** p value <0.01, * p value <0.05 The measure of efficacy was based on the reductions in total score of PANSS,13 and its Efficacy measures: Scores on Positive and
subscale items score namely-positive, negative negative symptom scale for schizophrenia
and general psychopathology subscales with 3 assesments done at 1 month, 3 months and 6months of treatment.
Table 2 shows the changes in total scores of PANSS as well as the changes in scores of its characterize demographic and clinical data of the subscales which include positive syndrome whole sample. The baseline and post treatment scale , negative syndrome scale and the general scores were analyzed by Paired t test. Univariate psychopathology scale from baseline to 1 month, analysis of variance was used for correlation baseline to 3 month and baseline to 6 month as purposes. Statistical significance was set at P < well as change from 1 month to 3 month and 0.05 level (significant) and P < 0.01 (highly from 3 month to 6 month.
As can be seen from the Table 2, the p values were highly significant on changes in the total scores as well as all three subscale scores at The olanzapine and the haloperidol group were all assessment points in both the olanzapine si mila r wi th r egar d t o so ciodemographic and the haloperidol group.
Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia Changes in PANSS score
Haloperidol group Positive syndrome score Negative syndrome score -5.45 -12.7 -15.6 -7.3 General psycho-pathology Compar ison of changes in PANSS scores at all assessment points bet ween
olanzapine and haloperidol gr oup.
Positive syndrome score Negative syndrome score General psycho-pathology score Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia Changes on ESRS
Table 4 show changes in ESRS domains comparison of changes in total score and the three from from baseline to 1 month, to 3 month and subscale scores between the olanzapine and to 6 month as well as change from 1 month to 3 haloperidol group did not reach statistical month and from 3 month to 6 month significance at all assessment points.
As can be seen from the table, there were Scores on Extrapyramidal symptom rating
no statistically significant changes in the scores of parkinsonism (both subjective andobjective examination) at all assessment The changes in ESRS is along its domains points in the olanzapine group. There were no namely, parkinsonism,dystonia and dyskinesia incidence of dyskinetic and dystonic movements (subjective) score, parkinsonism (objective) on objective examination at all assessment score, dystonia (objective) score and dyskinetic movements (objective) score and clinical globalimpression of dyskinesia, par kinsonism, But in the haloperidol group,there were akathisia and dystonia.
statistically significant changes in the scores of Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia parkinsonism(both subjective and objective up the patients for upto 6 months which is a fairly examination) at all assessment points. There long follow up in Indian settings.
were no incidence of dyskinetic and dystonic There was significant improvement on PANSS movements on objective examination at all tota l score, positiv e syndro me, nega tive assessment points.
syndrome and ge neral psycho pathology subscale scores at all points of comparisons in Comparison on ESRS scores between the two groups
the study in both olanzapine group and thehalo peridol group. On compa rison of the improvement in PANSS scores , the improvementon total as well as the 3 subscale scores in olanzapine group was more as compared to haloperidol but this difference failed to reach ** p<0.01 * p<0.05 statistical significance at all assessment points.
As can be seem from the Table 5, p values are Hence, the two drugs were equally efficacious in statistically significant in favour of haloperidol improving symptoms when assessed with group with regards to the mean increase in scores PANSS. These findings are in concordance with in domains of ESRS namely, parkinsonism findings of a a double blind randomized control subjective and objective examination across all trial14 comparing olanzapine and haloperidol in assessments points.
patients of schizophrenia which found substantialbut comparable baseline-to-endpoint reductions in symptom severity in both the groups, when The present study was carried out to compare followed up for a period of 104 weeks. Similarly, the efficacy of olanzapine versus haloperidol in a meta-analysis of three trials comparing patients of schizophrenia. The present study was olanzapine with haloperidol showed that changes a prospective, randomized, open label trial with in positive and negative symptom scores did not an intent to treat analysis in which patients who differ significantly between the two drugs.15 were drug naïve or who had not been on Another study examined the effectiveness of antipsychotics for atleast 2 weeks were started o la nzapine and ha lo pe ri do l in pat ie nt s either on olanzapine or haloperidol as per randomization. The doses of olanzapine were in schizophrenia-related psychotic disorder over a the range of 5-30 mg(mean dose 18.5 mg) and 2-year treatment period. 16 doses of haloperidol were in range of 5-15mg(mean dose 11.275 mg). All patients were Olanzapine and haloperidol treatment were assessed at baseline, at the end of 1 month, at both associated with comparable reductions in the end of 3 months and at the end of 6 months symptom severity over the course of the study.
using the PANSS. The majority of efficacy studies Similarly in a 12-month, multi-center, double- of the atypical antipsychotics that have been blind comparison of flexibly-dosed olanzapine and reported relate to symptom improvement in short- term clinical trials of less than 12 weeks in schizophrenia, authors found that olanzapine and duration.14,17,18 However, schizophrenia is often haloperidol did not differ in measures of efficacy.17 both a chronic and recurrent disorder and hence Similar results were obtained in an open label information on efficacy in long-term maintenance trial of 12 weeks duration on Indian patients where treatment is important. Hence, our study fol owed improvement in total and positive syndrome Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia scores of PANSS was similar in patients on either the appropriate role of the atypical antipsychotics olazapine or haloperidol.18 However, in the study, in treating schizophrenia. The debate concerns olanzapine showed superior improvement on the relative efficacy, the comparative side effects, negative symptoms and secondary depressive their effectiveness for patients in everyday settings features. This superiority of olanzapine in and their cost-effectiveness. The results from improving negative symptoms was not found in various studies have been conflicting. In the our study. The perceived benefits of atypical western market, the atypical antipsychotics cost antipsychotics on negative symptoms may result considerably more than the conventional drugs pr ima ri ly fro m dec rea sing the burden of they may replace.
extrapyramidal adverse effects rather than better The avera ge co st of olanzapine was efficacy for core negative symptoms.19 approximately Rs.1260 and that of haloperidol was The most recent trial comparing second approximately Rs.1080.but due to the addition of generation antipsychotic drugs(olanzapine, trihexyphenidyl which was used in haloperidol ziprasidone, quetiapine, amisulpride) with low- group, the cost in this group was approximately dose haloperidol in first-episode schizophrenia Rs.1700. If the additional costs of typical also found comparable reductions in PANSS antipsychotics in our setting are not justified by scores at end of 1 year.20 However, this study their benefits, this information could significantly used haloperidol in dose ranges of 1-4 mg which influence clinicians in their decision making in was much less than the dose used in our study(5- prescribing antipsychotics. There have been 15 mg). It has been hypothesized that low doses increasing focus on testing the efficacy of of antipsychotics suffice in first episode patients antipsychotics in real-world settings that would because first-episode patients have little mirror routine clinical care without strict inclusion exposure to antipsychotic medications, and so criteria and non-industry sponsored in order to their dopaminergic system may be more sensitive enhance the credibility of the study.
to antipsychotic medication. The similar efficacy Though the present study was conducted of haloperidol and olanzapine found in our study using sound methodology and strict inclusion is also echoing the findings of recent large, criteria, there are certain limitations. 1) The study multicentre randomized double blind, industry had a small sample size. 2) It was an open label independent controlled trials21,22 conducted in the trial and no blinding was done, hence personal west in real world settings that typical and bias of information cannot be ruled out. 3) We atypical antipsychotics are largely equally did not compare the discontinuation rates and efficacious and it is the side effect profile that reasons for discontinuation of patients who determines issues like discontinuation of dropped out from the treatment which could have treatment . This similar efficacy is of importance be en a n i mpor tant outco me meas ur e of in a developing country like ours where the cost comparison between the two drugs.
effectiveness of drugs is relevant and important In Conclusion conventional antipsychotic in issues of compliance and subsequent long term drugs are believed to be cheaper than the atypical management of patients . Hence we can observe antipsychotic drugs. Thus, majority of the that though various claims have been made with dispensaries in government hospitals still regard to the superiority in efficacy and safety of dispense conventional antipsychotics including the atypical antipsychotics as compared to the chlorpromazine, haloperidol and trifluperazine with conventional drugs, this has precipitated an the assumption of cost reduction. The findings of important debate that is now underway regarding Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia the study demo nstrat e tha t conventio nal J Clin Psychiatry 1978;39:807–814.
antipsychotic drugs are not cheaper, maybe 10. Settle EC, Ayd FJ. Haloperidol: a quarter century of slightly costlier than the atypicals. The study also experience. J Clin Psychiatry 1983;44:440–448.
supports the fact that conventional antipsychotics 11. World Health Organization. The ICD-10 classification lead to troublesome extrapyramidal side effects of Mental and Behavioral Di sorders : Clini calDescription and Diagnostic Guidelines. World Health which are subjectively as well as objectively Organization, Geneva; 1992.
causing social embarrassment for the patients.
12. Kane JM, Marder SR. P sychopharmacological On the other hand, atypicals are not as safe as treatment of schi zophr enia. Sc hizophr Bull they were thought to be. Treatment emergent metabolic syndrome with atypicals is a major 13. Kay SR, Fiszbein A, Opler LA. The positive and cause of concern for health professionals. They negative syndrome scale for schizophrenia (PANSS).
Schizophr Bull have started facing a dilemma of addressing the 1987; 13: 261-276.
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14. Lieberman JA, Tol efson G, Tohen M, Green AI, Gur RE, Kahn R et al. Comparative efficacy and safety ofatypical and conventional antipsychoticdrugs in first- episode psychosis: a randomized, double-blind trial Jablensky A. Epidemiology of schizophrenia: the global of olanzapine versus haloperidol. Am J Psychiatry burden of disease and disability. Eur Arch Psychiatry Clin Neurosci 2000; 250: 274 – 285.
15. Sauriol L, Laporta M, Edwardes MD, Deslandes M, Rossler W, Salize HJ, Van os J, Riecher- Rossler A.Size Ricard N, Suissa S et al. Meta-analysis comparing of burden of schizophrenia and psychotic disorders.
newer antipsychotic drugs for the treatment of Eur Neuropsychopharmacol 2005; 15: 399 – 409.
schizophrenia: evaluating the indirect approach. Clin Stone MH. History of sc hizophrenia and its antecedents. In: Lieberman JA,Stroup TS, Perkins DO, 16. Green AI, Lieberman JA, Hamer RM, Glick ID, Gur RE, eds. Textbook of Schizophrenia. Washington,DC: Kahn RS et al . Olanzapine and haloperidol in first American Psychiatric Publishing Inc;2006:1-15.
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JA.Treatments for schizophrenia: a critical review of 17. Rosenheck R, Perlick D, Bingham S, Liu-Mares W, pharmacology and mechanisms of action of Col ins J, Warren S et al for the Department of Veterans antipsychotic drugs. Mol Psychiatry 2005;10:79- Affairs Cooperative Study Group on the Cost- Effectiveness of Olanzapine. Effectiveness and cost Prien RF, Cole JO. High dose chlorpromazine therapy of olanzapine and haloperidol in the treatment of in chronic schizophrenia: report of National Institute schizophrenia: A randomized control ed trial. JAMA of Mental Health–psychopharmacology research br anch collaborati ve study gr oup. Ar ch G en 18. Avasthi A, Kulhara P .Olanzapine in the treatment of schizophrenia : an open label comparative clinical trial Davis J M. Overview: mai ntenance therapy in from north india .Indian J Psychiatry 2001;43:257- psyc hiatry, I: schizophreni a. Am J Psy chiatry 19. Glazer W M.Extrapyramidal side effects, tardive May PR, Tuma AH, Dixon WJ, Yale C, Thiele DA, Kraude dyskinesia, and the concept of atypicality. J Clin WH.Schizophrenia: a fol ow-up study of the results Psychiatry 2000;61(Suppl 3):S16-S21.
of five forms of treatment. Arch Gen Psychiatry 20. Kahn RS, Fleischhacker W W, Boter H, Davidson M, Vergouwe Y,Keet I P M et al for the EUFEST study Ayd FJ. Haloper idol: fi fteen years of c lini cal group. Effectiveness of antipsychotic drugs in first- experience. Diseases of the Nervous System epi sode schizophrenia and schizophr enif orm disorder:an open randomized clinical trial. Lancet2008; 371:1085-1097.
Ayd FJ. Haloperidol: twenty years' clinical experience.
Journal of Mental Health & Human Behavior, 2010 Dhar et al : Haloperidol & Olanzapine in Schizophrenia 21. Lieberman JA, Stroup TS, McEvoy JP, Swartz SM, Hayhurst KP et al.Randomized control ed trial of the Rosenheck AR, Perkins DO et al. Effectiveness of effect on quality of life of second- vs first-generation antipsychotic drugs in patients wi th c hronic antipsychotic drugs in schizophrenia: cost utility of schizophrenia. N Engl J Me .
d 2005;353:1209-1223.
the latest antipsychotic drugs in schizophrenia study Arch Gen Psychiatry 22. Jones PB, Barnes TRE, Davies L, Dunn G, Lloyd H, Romika Dhar, Formerly Senior ResidentB. S. Chavan, Professor & HeadAjeet Sidana, Assistant ProfessorDepartment of Psychiatry,Govt. Medical College & Hospital,Sector 32, Chandigarh Corresponding Author:
Romika Dhar
# 8, Swastik Vihar, Phase I,
Mansa Devi Complex, Sector 5,
Panchkula
Email: romika_dhar@yahoo.com
Journal of Mental Health & Human Behavior, 2010

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