Article Identification
Article Title: Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine
Authors:
- Nirmal S Raveendran, Lecturer, Department of Psychiatry, Christian Medical College, Vellore
- Prathap Tharyan, Professor, Department of Psychiatry, Christian Medical College, Vellore
- Jacob Alexander, Lecturer, Department of Psychiatry, Christian Medical College, Vellore
- Clive Elliot Adams, Associate Professor, BV Moses Centre for Clinical Trials and Evidence-Based Medicine, Christian Medical College, Vellore
Journal Name: BMJ (British Medical Journal)
Year: 2007
Volume: Not specified
Issue: Not specified
Type of Study: Pragmatic, concealed allocation, randomised controlled trial
DOI/PMID: 10.1136/bmj.39341.608519.BE; Clinical Trials NCT00455234
Quick Reference Summary
- Both intramuscular olanzapine and intramuscular haloperidol plus promethazine were similarly effective in achieving tranquillity or sleep in agitated or violent psychiatric patients within 15 minutes (olanzapine 87%, haloperidol plus promethazine 91%; relative risk 0.96, 95% CI 0.34 to 1.47).
- Olanzapine was associated with a higher requirement for additional medical interventions within four hours (21% vs 43% for haloperidol plus promethazine; relative risk 2.07, 95% CI 1.43 to 2.97).
Core Clinical Question
Does intramuscular olanzapine compare to intramuscular haloperidol plus promethazine in effectively achieving rapid tranquillisation in agitated or violent psychiatric patients within emergency settings in India?
Background
Disease or Condition Overview:
- Approximately 15 million people in India suffer from serious mental disorders.
- Agitated or violent behavior, often stemming from severe mental illness or substance misuse, accounts for around 10% of emergency psychiatric services globally.
Prior Data on the Topic:
- Intramuscular haloperidol and promethazine combined is widely utilized for rapid tranquillisation in low and middle-income countries like India and Brazil.
- Previous pragmatic trials have demonstrated the efficacy and safety of this combination in managing acute agitation.
Current Standard of Care:
- Non-pharmacological strategies are recommended for managing violence in psychiatric emergencies.
- Pharmacological rapid tranquillisation varies, with haloperidol and promethazine being common choices influenced by local practices rather than robust evidence.
Knowledge Gaps Addressed by Study:
- Limited evidence comparing the efficacy and safety of intramuscular olanzapine versus the established combination of haloperidol and promethazine in Indian emergency psychiatric settings.
Study Rationale:
- Given the high prevalence of mental illness-related emergencies in India and the reliance on haloperidol-promethazine, it is essential to evaluate alternative treatments like olanzapine for rapid tranquillisation.
Methods Summary
- Study Design: Pragmatic, concealed allocation, randomised controlled trial.
- Setting and Time Period: Emergency psychiatry department of a general hospital in Vellore, South India. Published in 2007; exact study period not specified.
- Population Characteristics: 300 adults presenting with agitated or violent behavior due to mental illness or substance misuse.
- Inclusion Criteria: Adults presenting with agitated or violent behavior necessitating rapid tranquillisation.
- Exclusion Criteria: Not specified in provided text.
- Intervention Details: Intramuscular olanzapine administered as per standard dosing protocols.
- Control/Comparison Group Details: Intramuscular haloperidol plus promethazine administered as per standard dosing protocols.
- Primary and Secondary Outcomes:
- Primary Outcome: Proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes.
- Secondary Outcomes: Proportion tranquil, asleep, restrained, absconding, or clinically improved at 15, 30, 60, 120, and 240 minutes; additional medical interventions and adverse effects within four hours; compliance with oral drugs and adverse effects over two weeks.
- Statistical Analysis Approach: Relative risk calculations with 95% confidence intervals; significance testing likely performed but specifics not provided.
- Sample Size Calculations: Not specified in provided text.
- Ethics and Funding Information: Not detailed in provided text.
Detailed Results
Participant Flow and Demographics:
- Total Participants Randomised: 300 (150 to intramuscular olanzapine, 150 to intramuscular haloperidol plus promethazine)
- Follow-Up Data Available: 298 (99% completion rate)
- Demographics: Not detailed in provided text.
Primary Outcome Results:
- Tranquil or Asleep at 15 Minutes:
- Olanzapine: 131/150 (87%)
- Haloperidol plus Promethazine: 136/150 (91%)
- Relative Risk: 0.96 (95% CI 0.34 to 1.47)
- Tranquil or Asleep at 240 Minutes:
- Olanzapine: 144/150 (96%)
- Haloperidol plus Promethazine: 145/150 (97%)
- Relative Risk: 0.99 (95% CI 0.95 to 1.03)
Secondary Outcome Results:
- Additional Medical Interventions within Four Hours:
- Olanzapine: 65/150 (43%)
- Haloperidol plus Promethazine: 31/150 (21%)
- Relative Risk: 2.07 (95% CI 1.43 to 2.97)
- Adverse Events/Safety Data:
- Adverse effects were uncommon in both treatment groups.
Effect Sizes and Confidence Intervals:
- Primary outcomes showed no significant difference between treatments.
- Olanzapine group required significantly more additional interventions.
Subgroup Analyses:
- Not detailed in provided text.
Adverse Events/Safety Data:
- Both treatments were generally safe with uncommon adverse effects.
Results Tables:
| Outcome | Olanzapine Group | Haloperidol + Promethazine Group | Difference (95% CI) | P-value |
|---|---|---|---|---|
| Tranquil or Asleep at 15 Minutes | 131/150 (87%) | 136/150 (91%) | Relative Risk 0.96 (0.34 to 1.47) | Not specified |
| Tranquil or Asleep at 240 Minutes | 144/150 (96%) | 145/150 (97%) | Relative Risk 0.99 (0.95 to 1.03) | Not specified |
| Required Additional Medical Interventions within 4 Hours | 65/150 (43%) | 31/150 (21%) | Relative Risk 2.07 (1.43 to 2.97) | Not specified |
Authors' Conclusions
Primary Conclusions:
- Both intramuscular olanzapine and intramuscular haloperidol plus promethazine are effective for rapid tranquillisation in agitated or violent psychiatric patients.
Authors' Interpretation of Results:
- Despite similar efficacy in achieving tranquillity or sleep, olanzapine was associated with a higher need for additional medical interventions within four hours.
Clinical Implications Stated by Authors:
- While both treatments are viable options, the increased requirement for additional interventions with olanzapine may influence clinical decision-making.
Future Research Recommendations:
- Not explicitly stated in provided text.
Critical Analysis
A. Strengths:
Methodological Strengths:
- Randomised controlled design enhances internal validity.
- High follow-up completion rate (99%) minimizes attrition bias.
Internal Validity Considerations:
- Concealed allocation reduces selection bias.
External Validity Considerations:
- Pragmatic design enhances generalizability to real-world settings in similar low and middle-income countries.
B. Limitations:
Study Design Limitations:
- Lack of blinding may introduce performance or detection bias.
Potential Biases:
- Absence of detailed demographic data limits assessment of confounding factors.
Generalizability Issues:
- Results primarily applicable to emergency psychiatric settings in India; may not generalize to other populations or settings.
Statistical Limitations:
- Confidence intervals for primary outcomes are wide, indicating uncertainty.
Missing Data Handling:
- Minimal missing data reported (2 out of 300 participants).
C. Literature Context
(As discussed explicitly in the provided text)
A. Previous Studies and Meta-Analyses:
- Study in India: Raveendran et al. Rapid tranquillisation-clinical trial in India. (Reference: Not fully provided)
- Study in Brazil: Similar combination of haloperidol and promethazine proved efficacy and safety in 250 agitated or violent individuals compared to benzodiazepines. (Reference: Not fully provided)
B. Contrasting Methodological Quality:
- Current Study vs. Previous Trials: Both current and previous studies used pragmatic designs suitable for low and middle-income settings. Differences in sample sizes and specific settings may impact comparability. (References: Not fully provided)
C. Comparisons with Guidelines:
- UK’s National Institute for Health and Clinical Excellence (NICE) Guidelines (Year Not Specified): Provide recommendations for managing violence in psychiatric emergencies. Emphasize consensus statements over robust evidence due to variability in clinical practice. (Reference: Not fully provided)
D. This Trial's Contribution:
- Addition to Existing Evidence: Provides direct comparison between olanzapine and the established haloperidol-promethazine combination in the context of Indian emergency psychiatric settings. Highlights the higher need for additional interventions with olanzapine despite similar primary outcomes. (Reference: Not fully provided)
Clinical Application
- Impact on Current Practice: Both intramuscular olanzapine and haloperidol plus promethazine can be effectively used for rapid tranquillisation; however, clinicians should be aware of the higher likelihood of requiring additional interventions with olanzapine.
- Specific Patient Populations or Scenarios: Findings are most applicable to agitated or violent psychiatric patients in emergency settings within similar low and middle-income healthcare environments.
- Implementation Considerations:
- Availability of resources to manage potential additional interventions when using olanzapine.
- Training for staff on recognizing and addressing the need for supplementary treatments.
- Integration with Existing Evidence: Aligns with previous studies supporting the efficacy of haloperidol-promethazine while providing comparative data for olanzapine.
How To Use This Info In Practice
Practitioners can consider using either intramuscular olanzapine or haloperidol plus promethazine for rapid tranquillisation, keeping in mind the potential need for additional interventions with olanzapine.
Notes for Clarity
- Statistical Significance: Differences in additional medical interventions between groups are statistically significant (p < 0.05).
- Confidence Intervals: Provided for relative risks, enhancing understanding of effect precision.
- Conflicts of Interest: Not specified in provided text.
- Areas of Uncertainty: Limited data on long-term outcomes and specific adverse effects beyond four hours.
- Number Needed to Treat/Harm: Not provided in the study.
- Post-Hoc Analyses: Not indicated.
- Funding Sources: Not detailed in provided text.