EXTRAPYRAMIDAL SIDE-EFFECTS OF ANTYPSYCHOTIC IN A RANDOMISED TRIAL

Mira Arlita Rahmawati Riduan Adoro Lumban Gaol Jeannette Diana Rheny Giovanny Otniel Budi Krisetya Jonggi Mathias Riizky Syawaluddin Djamal Puspita Ayu Margaretha 07-70 08-33 08-35 08-36 08-39 08-42 08-43 08-44

background
There are claims that secondgeneration antipsychotic produce fewer extrapyramidal side-effects (EPS) compared with firstgeneration drugs

aims
To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia

method

Analysis for concominant medication or treatment discontinuation for EPS events, using a standarised rating scale also change in rating scales from baseline

results
There were no significant

differences in incidence for parkinsonism, dystonia, akathisia, or tardive dyskinesia when comparing second-generation antipsychotic with perphenazine

 Concomitant antiparkinsonism medications: Greater rates, people with risperidone Lower rates, people with quetiapine

1 olanzapine (discontinued)
1perphenazine

Acute dystonia

Only 8 cases reported

1 quetiapine (discontinued) 2 risperidone (1 discontinued) 3 ziprasidone (2 discontinued)

Parkinsonism
Statistical anylisis showed no statistically significant difference between treatment groups Covariate-adjusted 12-month event rates were notable at 37-44 % for 4 secondgeneration antipsychotic and 37 % for perphenazine. Only 2 patients discontinued treatment for EPS within the first month

Analysis of probability of having a parkinsonism event within 1 year for people wi

` Olanzapine Perphenazine Quetiapine Risperidone Ziprasidone

Data-set

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Overall P

Paired comparison

I: P v. O v. Q v. Rc

174

0.38 (0.30 0.47)

160

0.37 (0.29 0.48)

166

0.35 (0.27 0.45)

167

0.424 (0.34 0.52)

0.649

NS

II: O v. Q v. Rd

201

0.382 (0.30 0.47)

187

0.368 (0.29 0.46)

191

0.440 (0.36 0.54)

0.38

NS

III: Z v. O, Q, Re

113

0.46 (0.35 0.58)

106

0.41 (0.30 0.54)

104

0.47 (0.36 0.59)

98

0.42 (0.31 0.56)

0.85

NS

IV: Z v. Pf

92

0.42 (0.30 0.58)

87

0.467 (0.33 0.63)

0.63

NS

Akathisia
Poisson regression analysis revealed no significant difference between groups Covariate-adjusted 12-months events rate ranged from 26%-35% for the secondgeneration antipsychotic and 35% for perphenazine.

Analysis of probability of having an akathisia event within 1 year for people with no
Olanzapine Perphenazine Quetiapine Risperidone Ziprasidone

Data-set

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Estimated probablity (95% CI)

Overall P

Paired comparison

I: P V. O V. Q V. Rc

197

0.26 (0.20 0.33)

207

0.35 (0.28 0.43)

207

0.26 (0.20 0.35)

209

0.35 (0.28 0.44)

0.10

NS

II: O V. Q V. Rd

238

0.260 (0.20 0.337)

250

0.277 (0.21 0.367)

244

0.342 (0.26 0.43)

0.20

NS

III: Z V. O, Q, Re

118

0.21 (0.13 0.32)

143

0.25 (0.16 0.37)

123

0.38 (0.27 0.52)

130

0.31 (0.22 0.44)

0.07

NS

IV: Z V. Pf

118

0.41 (0.31 0.53)

110

0.30 (0.20 0.42)

0.16

NS

Tardive Dyskinesia
Poisson regression revealed no statistically significant difference between treatment groups Covariate-adjusted 12-month event rates for Schooler-Kane TD ranged from 0,7%2,2% for the second-generation antypsychotic, 2,7% for perphenazine.

Analysis of probability of having a tardive dyskinesia event within 1 year for people
Olanzapine Data-set n Estimated probablity (95% CI) Perphenazine N Estimated probablity (95% CI) N Quetiapine Estimated probablity (95% CI) N Risperidone Estimated probablity (95% CI) n Ziprasidone Estimated probablity (95% CI) Overall P Paired comparison

I: P v. O v. Q v. Rc

Schooler Kane

182

0.01 (0.002 0.03)

183

0.03 (0.01 0.07)

179

0.02 (0.001 0.06)

179

0.01 (0.004 0.04)

0.25

NS

Modified Schooler Kane 216 0.13 (0.08 0.19) 221 0.22 (0.15 0.30) 222 0.13 (0.08 0.21) 220 0.15 (0.10 0.23) 0.22 NS

III: Z v. P, O, Q, Rd

Schooler Kane

102

0.01 (0.001 0.06)

102

0.04 (0.01 0.12)

104

0.04 (0.01 0.12)

96

0.03 (0.010 0.10)

89

0.02 (0.005 0.09)

0.47

NS

Modified Schooler Kane 122 0.17 (0.10 0.28) 128 0.23 (0.15 0.36) 128 0.15 (0.08 0.28) 121 0.18 (0.11 0.30) 124 0.14 (0.08 0.26) 0.74 NS

discussion

Comparison with previous studies examinig eps between second and first generation antipsychotic
Evidence from various clinical trials indicate that motor abnormalities me be aggravated by firstgeneration antipsychotic than second-generation. Review by Correll et al: tardive dyskinesia by secondgeneration (0,8%) compared with first-generation (5,4%), 3 of trial used haloperidol in high mean dose (13-15 mg) that may have biased the review

The previous trial, individu who were experiencing EPS syndrome were excluded. In the current analysis, only individuals without tardive dyskinesia at baseline can included for comparison between secondgeneration antipsychotic and perphenazine

Higher treatment discontinuation with perphenazine

conclusion

The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.

Critical appraisal

Title : Extrapyramidal Side-Effects of Antipsychotic in a Randomised Trial

The title consisting 9 words of a journal title., and straight to the point of the theme of the journal.

Critical appraisal

Abstract and introduction:

The abstract had been providing with significant point that understandable. Theres no introduction so if we dont understand the basic, we should read it in another books.

Critical appraisal

Method
Analysis for concomitant medication or treatment discontinuation for EPS events, using a standarised rating scale also change in rating scales from baseline.
The baseline cant be understand because there arent more explanation about baseline is.

Critical appraisal

Result
There were no significant differences in incidence for parkinsonism, dystonia, akathisia, or tardive dyskinesia when comparing second-generation antipsychotic with perphenazine
The result was presented very well as it mostly presented in table to be easily read

Analysis of Adverse Drug Reaction of Atypical Antipsychotic Drugs in Psychiatry OPD

background

Novel atypical and conventional atypical antipsychotic can reduce both positive and negative symptoms of schizophrenia. However, these drugs have separate set of adverse drugs reactions (ADRs). This study will review about ADRs, which can have impact on long-term compliance and achieving successful treatment

Material & methods

Patient from psychiatry outpatient department and psychotic patient prescribed atypical antipsychotic drugs is analysed thourgh a prospective study Questionnaire also used and recorded in the case record form

results

Majority of the ADRs were seen with risperidone and olanzapine. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of total events.

Gastrointestinal and sleep disturbance observed within 7days to 2-3 months after treatment EPS, fatigue, seizure observed after longterm (3-9 months) use

discussion
Number of times atypical antipsychotics were prescribed and adverse events associated with it

risperidone
Gastrointestinal, sleep distrubance observed within 7 days to 2-3 months after treatment EPS, fatigue, seizure and dizziness observed after longterm (3-9 months) use

All ADRs therapeutic dose (4 mg/day), except EPS, seizure and hypersalivation occurred at dose of 6 mg/day
EPS dose reduction and adding central anticholinergic

Risperidone alone on 25 occasions, ADR occurred in 11 cases

Risperidone combined with central anticholinergic, ADR occurred 4 out of 13 cases

olanzapine
Gastrointestinal and sleep disturbance observed within 7 days to 2-3 months after treatment

EPS, seizure, and increased frequency of micturition observed on long-term 6 months-1 year

Initial dose of olanzapine is 5 mg/day, gradually increased up tp maximum 20 mg/day All ADRs reported here found with the dose range of 10-15 mg/day

clozapine

events with clozapine were gastrointestinal disturbance, hypersalivation, dizziness and fatigue

Adverse

Causality of ADR by Naranjo's scale

Weight Gain

o o

Significant if it exceeds 7 % of the initial weight after 10 weeks Meyer older patients (>60 YO) lower than younger adults

Sleep Disturbance

US product somnolence is a common ADR with atypical antipsychotic Incidence varies from 5 to 39% Olanzepin cause both somnolence as well as insomnia. Somnolence was more frequent in patients with olanzepine than with risperidone

Anticholinergic Side Effects

Anticholinergic side effects like dizziness, constipation, palpitation and hypersalivation accounted for 15,03% of the total ADRs.

Clozapine (4 in 6 cases)
Olanzapine (8 in 34 cases) Risperidone (3 in 38 cases)

conclusion

The present study thus adds to the existing information on prevalence of adverese effects to atipycal antipsychotic drugs. Role and of active surveillance in post-marketing phase is emphasized

critical appraisal

Title

Analysis of Adverse Drug Reactions of Atypical Antipsychotic Drugs in Psychiatry OPD The title has a straight to the point theme

Abstract and introduction:

The abstract had been providing with significant point that understandable. Consisting with all the nessesary point Introduction provided by the resource with enough information so that the reader could know the differences between 2 classes of antipsychotic drugs.

Critical appraisal

Method: analysis for ADRs of the atypical antipsychotic is using a longitudinal prospective obeservational and a questionnaire as an addition

Critical appraisal

Result:
The majority of the adverse events were seen with risperidone and olanzapine How are the results presented? The results was presented very good with a simple word and and the appearance of table so that easly to be read and understand