Journal Presentation on efficacy of monotherapy in Bipolar Disorder Lithium vs. Valproate vs. Olanzapine vs. Quetiapine

1. Journal Presentation
Dr. Ahsan Aziz
Assistant Registrar, NIMH.

2. Title
Lithium vs. valproate vs. olanzapine vs.
quetiapine as maintenance monotherapy for
bipolar disorder: a population-based UK cohort
study using electronic health records

3. Publication
World Psychiatry
Official Journal of World Psychiatric
Association
February 2016
Citation: 42

4. Authors
Joseph F. Hayes
Louise Marston
Kate Walters
John R. Geddes
Michael King
David P.J. Osborn
University College London

5. Introduction
Bipolar disorder runs a chronic course.
6th most common cause of disability in the
world.

6. Research Aim
Compare rates of monotherapy treatment
failure in individuals prescribed lithium,
valproate, olanzapine or quetiapine by a
population-based cohort study using electronic
health records.

7. Study Design
Prospective population based cohort study
using electronic health record.

8. Study Subjects
UK primary health care data for 11 million people
was searched.
14,396 were diagnosed as Bipolar Disorder.
Among them 5,089 were prescribed monotherapy
of the above mentioned drugs.
Lithium =1,505; valproate =1,173; olanzapine
=1,366 and quetiapine =1,075 people.

9. Study Subjects
Inclusion criteria
Bipolar patient receiving monotherapy
between the period of 1st January, 1995 to
31st December, 2013.

10. Study Subjects
Exclusion criteria
– If they received diagnosis of schizophrenia
any time
– If they were prescribed any other study drug
– If they were added another mood stabilizer, anti-
psychotic, anti-depressant and benzodiazepine
– Death of the patient
– Leaving GP practice

11. Treatment Failure
Stopping index medication. (tolerability issue)
or
Requiring add-on of a mood stabilizer,
antipsychotic, antidepressant or
benzodiazepine. (efficacy issue)

13. Statistical Technique Used
Propensity Score was used to match different
cohorts.
Cox Regression Analysis was used to compare
Rate of drug stopping
Add on of another drugs
The proportional hazard model was used to
calculate Hazard Ratio (HR)

14. Results
Treatment failure had occurred in 75% of those
prescribed
Lithium by 2.05 years (95% CI: 1.63-2.51)
Quetiapine by 0.76 years (95% CI: 0.64-0.84)
Valproate by 0.98 years (95% CI: 0.84-1.18)
Olanzapine by 1.13 (95% CI: 1.00-1.31)

15. Results

16. Results

17. Results

18. Results

19. Conclusion
Lithium monotherapy is more efficacious and
tolerable than other drugs.

20. Limitation described by authors:
Prescribing drug doesn’t ensure patient has taken
medication.
Possible confounding variable
Individual GP’s choice of drug
Physical health variable
Aripiprazole and Lamotrigine weren’t considered
because of too small sample size.

21. Critical Appraisal
Largest head to head comparison of four most
commonly used drugs.
Treatment failure is defined as stopping the
drug.

22. Similar studies
1. Lithium is more effective than placebo for preventing
all relapses in patients with bipolar but not unipolar
disorder (burgess et al)
Relative Risk Reduction=40% and NNT=4
2. Lithium plus valproate combination therapy versus
monotherapy for relapse prevention in bipolar I
disorder (Geddes et al)
HR of 1.41 95% CI (1-1.91)

23. Thank You