Newer drugs for treatment of mania associated with bipolar affective disorder

210 Pages·2004·0.73 MB·English

Health Technology Assessment 2004;Vol. 8: No. 19
A rapid and systematic review and
economic evaluation of the clinical and
cost-effectiveness of newer drugs for
treatment of mania associated with
bipolar affective disorder
C Bridle, S Palmer, A-M Bagnall, J Darba,
S Duffy, M Sculpher and R Riemsma
May 2004
HTA
Health Technology Assessment
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A rapid and systematic review and
economic evaluation of the clinical and
cost-effectiveness of newer drugs for
treatment of mania associated with
bipolar affective disorder
1 2 1 2
C Bridle, S Palmer, A-M Bagnall, J Darba,
1 2 1*
S Duffy, M Sculpher and R Riemsma
1 Centre for Reviews and Dissemination, University of York, UK
2 Centre for Health Economics, University of York, UK
*Corresponding author
Declared competing interests of authors:Stephen Palmer, Mark Sculpher and Josep
Darba have personal, non-specific interests as they have received consultancy and/or
research funding from the manufacturers of the drugs considered in this review. Stephen
Palmer has undertaken consultancy for AstraZeneca and Eli Lilly on unrelated products.
Mark Sculpher has undertaken consultancy for AstraZeneca on unrelated products. Josep
Darba has undertaken consultancy for Sanofi-Synthelabo on unrelated products. Other
members of the team undertaking HTA reviews within the Centre for Health Economics
have received consultancy and/or research funding from the manufacturers of the drugs
considered in this review, but these individuals were not involved in this report and have
not worked on any of the drugs considered in this review. Rob Riemsma is also a member
of the editorial board for Health Technology Assessment, although he was not involved in
the editorial process for this report.
Published May 2004
This report should be referenced as follows:
Bridle C, Palmer S, Bagnall A-M, Darba J, Duffy S, Sculpher M, et al. A rapid and
systematic review and economic evaluation of the clinical and cost-effectiveness of newer
drugs for treatment of mania associated with bipolar affective disorder. Health Technol
Assess2004;8(19).
Health Technology Assessmentis indexed in Index Medicus/MEDLINE and Excerpta Medica/
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Health Technology Assessment2004; Vol. 8: No. 19
Abstract
A rapid and systematic review and economic evaluation of the
clinical and cost-effectiveness of newer drugs for treatment of
mania associated with bipolar affective disorder
C Bridle,1 S Palmer,2 A-M Bagnall,1 J Darba,2 S Duffy,1 M Sculpher2
and R Riemsma1*
1Centre for Reviews and Dissemination, University of York, UK
2Centre for Health Economics, University of York, UK
*Corresponding author
Objectives: To evaluate the clinical and cost- criteria were not met in most trials. Quetiapine,
effectiveness of quetiapine, olanzapine and valproate olanzapine and valproate semisodium appear superior
semisodium in the treatment of mania associated with to placebo in reducing manic symptoms, but may cause
bipolar disorder. side-effects. There appears to be little difference
Data sources: Electronic databases; industry between these treatments and lithium in terms of
submissions made to the National Institute for Clinical effectiveness, but quetiapine is associated with
Excellence. somnolence and weight gain, whereas lithium is
Review methods: Randomised trials and economic associated with tremor. Olanzapine as adjunct therapy
evaluations that evaluated the effectiveness of to mood stabilisers may be more effective
quetiapine, olanzapine or valproate semisodium in the than placebo in reducing mania and improving global
treatment of mania associated with bipolar disorder health, but it is associated with more dry mouth,
were selected for inclusion. Data were extracted by somnolence, weight gain, increased appetite, tremor
one reviewer into a Microsoft Access database and and speech disorder. There was little difference
checked for quality and accuracy by a second. The between these treatments and haloperidol in reducing
quality of the cost-effectiveness studies was assessed mania, but haloperidol was associated with more
using a checklist updated from that developed by extrapyramidal side-effects and negative implications
Drummond and colleagues. Relative risk and mean for health-related quality of life. Intramuscular
difference data were presented as Forest plots but only olanzapine and lorazepam were equally effective and
pooled where this made sense clinically and statistically. safe in one very short (24 hour) trial. Valproate
Studies were grouped by drug and, within each drug, semisodium and carbamazepine were equally effective
by comparator used. (cid:2)2tests of heterogeneity were and safe in one small trial in children. Olanzapine may
performed for the outcomes if pooling was indicated. be more effective than valproate semisodium in
A probabilistic model was developed to estimate reducing mania, but was associated with more dry
costs from the perspective of the NHS, and mouth, increased appetite, oedema, somnolence,
health outcomes in terms of response rate, based speech disorder, Parkinson-like symptoms and weight
on an improvement of at least 50% in a patient’s gain. Valproate semisodium was associated with more
baseline manic symptoms derived from an interview- nausea than olanzapine.
based mania assessment scale. The model evaluated The results from the base-case analysis demonstrate
the cost-effectiveness of the alternative drugs when that choice of optimal strategy is dependent on the
used as part of treatment for the acute manic maximum that the health service is prepared to
episode only. pay per additional responder. For a figure of less
Results: Eighteen randomised trials met the inclusion than £7179 per additional responder, haloperidol
criteria. Aspects of three of the quetiapine studies were is the optimal decision; for a spend in excess of this,
commercial-in-confidence. The quality of the included it would be olanzapine. Under the most favourable
trials was limited and overall, key methodological scenario in relation to the costs of responders iii
© Queen’s Printer and Controller of HMSO 2004. All rights reserved.
Abstract
and non-responders beyond the 3-week period the cost-effectiveness analysis exist, which inevitably
considered in the base-case analysis, the incremental means that the results should be treated with some
cost-effectiveness ratio of olanzapine is reduced caution. There remains a need for well-conducted,
to £1236. randomised, double-blind head-to-head comparisons of
Conclusions: In comparison with placebo, quetiapine, drugs used in the treatment of mania associated with
olanzapine and valproate semisodium appear superior bipolar disorder and their cost-effectiveness. Participant
in reducing manic symptoms, but all drugs are demographic, diagnostic characteristics, the treatment
associated with adverse events. In comparison with of mania in children, the use of adjunctive therapy and
lithium, no significant differences were found between long-term safety issues in the elderly population, and
the three drugs in terms of effectiveness, and all were acute and long-term treatment are also subjects for
associated with adverse events. Several limitations of further study.
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Health Technology Assessment2004; Vol. 8: No. 19
Contents
Glossary and list of abbreviations ............. vii 5 Economic model ......................................... 75
Introduction ............................................... 75
Executive summary .................................... xi Methods ...................................................... 75
Results ........................................................ 83
1 Background ................................................ 1
Introduction ............................................... 1 6 Discussion ................................................... 89
Description and diagnosis .......................... 1 Main results ................................................ 89
Epidemiology and aetiology ...................... 1 Assumptions, limitations and
Course and outcome .................................. 2 uncertainties ............................................... 92
Treatment of mania .................................... 2 Implications for research ........................... 93
Description of new interventions ............... 2 Cost-effectiveness ....................................... 94
The present review ..................................... 3 Recommendations for further
research ...................................................... 95
2 Methods ..................................................... 5
Search strategy ........................................... 5 7 Conclusions ................................................ 97
Inclusion and exclusion criteria ................. 5 Clinical effectiveness .................................. 97
Data extraction strategy ............................. 6 Cost-effectiveness ....................................... 97
Quality assessment strategy ....................... 6
Methods of analysis/synthesis ..................... 6 Acknowledgements .................................... 99
Methods of analysis for economic
studies ......................................................... 6 References .................................................. 101
Key to quadrants ........................................ 7
Appendix 1 Search strategy ...................... 111
3 Effectiveness results ................................... 9
Quantity of research available .................... 9 Appendix 2 Excluded studies .................... 115
Quetiapine (Seroquel®) .............................. 9
Olanzapine (Zyprexa®) ............................... 20 Appendix 3 Details about data
Valproate semisodium (divalproex) ............ 39 extraction ................................................... 123
4 Economic review ........................................ 65 Appendix 4 Quality assessment criteria for
Summary of studies included in the randomised controlled trials of clinical
cost-effectiveness review ............................. 65 effectiveness ................................................ 125
Review of Keck and colleagues (1996).
A pharmacoeconomic model of valproate Appendix 5 Quality assessment
semisodium vs lithium in the acute and criteria for studies of
prophylactic treatment of bipolar I cost-effectiveness ........................................ 127
disorder ...................................................... 65
Review of Zajecka and colleagues (2000). Appendix 6 Data extraction tables –
Valproate semisodium vs olanzapine clinical effectiveness ................................... 129
for the treatment of mania in bipolar
disorder ...................................................... 67 Appendix 7 Quality assessment –
Review of the AstraZeneca clinical effectiveness ................................... 167
submission .................................................. 67
Review of the Eli Lilly submission ............. 67 Appendix 8 Data extraction tables for
Review of the Sanofi-Synthelabo economic evaluations ................................. 171
submission .................................................. 71
Summary of findings from the Appendix 9 Details of quality assessment
cost-effectiveness review ............................. 74 for economic studies .................................. 175
v
Contents
Appendix 10 WinBUGS model ................. 183 Health Technology Assessment reports
published to date ....................................... 189
Appendix 11 Cost assumptions applied to
sensitivity analysis ....................................... 185 Health Technology Assessment
Programme ................................................ 197
vi
Health Technology Assessment2004; Vol. 8: No. 19
Glossary and list of abbreviations
Technical terms and abbreviations are used throughout this report. The meaning is usually clear from
the context, but a glossary is provided for the non-specialist reader. In some cases, usage differs in the
literature, but the term has a constant meaning throughout this review.
Glossary
Abnormal Involuntary Movement Scale This Brief Psychiatric Rating Scale This is used to
has been used to assess tardive dyskinesia, a assess the severity of abnormal mental state.
long-term, drug-induced movement disorder. The original scale has 16 items, but a revised
It can be used to assess some short-term 18-item scale is commonly used. Each item is
movement disorders such as tremor. defined on a seven-point scale varying from
‘not present’ to ‘extremely severe’, scoring from
Agitated Behaviour Scale Developed to allow
0 to 6 or from 1 to 7. Scores can range from 0
objective assessment of agitated behaviour in
to 126, with high scores indicating more severe
traumatic brain injury patients. A 14-item
symptoms.
scale, with each item scored 1–4. Higher scores
indicate greater agitation. Clinical Global Impression Scale This scale
has been used to assess the overall condition of
Akathisia A movement disorder characterised
a mentally ill person – both severity of illness
by subjective feelings of inner restlessness,
and clinical improvement – by comparing
mental unease or dysphoria.
those conditions of investigated patients with
Anticholinergic Drugs which act to suppress those of other patients with the same diagnosis.
side-effects of the antipsychotic drugs related An eight-point (0–7) scoring system has been
to acetylcholine. used, with low scores indicating decreased
severity and/or overall improvement.
Antiparkinsonian Drugs which act to suppress
the movement disorder or ‘parkinsonian’ side- Cost–utility analysis Estimates of the
effects of antipsychotic drugs, such as poverty additional cost per quality-adjusted life-year
of movement and tremor (these symptoms can (QALY) saved or gained.
be similar to those seen in Parkinson’s disease).
Extrapyramidal syndrome/symptoms A type
Atypical antipsychotic Drugs which aim to of movement disorder which can be a side-
treat the psychotic symptoms of schizophrenia effect of antipsychotic drugs.
but which are thought to cause fewer
Extrapyramidal Symptom Rating Scale This
movement disorder side-effects than typical
consists of a questionnaire relating to
antipsychotics. Atypical antipsychotics tend to
parkinsonian symptoms (nine items), a
be newer and therefore more expensive than
physician’s examination for parkinsonism and
typical antipsychotics. The only definition for
dyskinetic movements (eight items), and a
‘atypicality’ relates to catalepsy in rats.
clinical global impression of tardive dyskinesia.
Barnes Akathisia Scale The scale comprises High scores indicate severe levels of movement
items rating the observable, restless movements disorder.
that characterise akathisia, a subjective
Global Assessment of Functioning Scale A
awareness of restlessness, and any distress
graduated continuum (varying between 0 and
associated with the condition. These items are
100) from psychological or psychiatric sickness
rated from 0 = normal to 3 = severe. In
to health.
addition, there is an item for rating global
severity (from 0 = absent to 5 = severe). A low
score indicates low levels of akathisia. continued
vii
© Queen’s Printer and Controller of HMSO 2004. All rights reserved.
Glossary and list of abbreviations
Glossary continued
Global Assessment Scale Used to evaluate the measuring the severity of general
overall functioning of a person during a psychopathology, positive symptoms (PANSS-P)
specified period in terms of psychological well- and negative symptoms (PANSS-N). A low
being or sickness. Time period assessed is score indicates lesser severity.
generally 1 week prior to evaluation. The scale
Positive symptoms Symptoms of schizophrenia
covers the entire range of severity and can be
such as hallucinations and delusions.
used in any situation or study where an overall
evaluation of the severity of the illness or Publication bias The tendency for studies
degree of health is needed. which show a positive effect to be published
more readily than those which show no effect
Hamilton Depression Rating Scale A scale
for a particular intervention.
generally used in psychopharmaceutical studies
with depressed patients. Various versions exist Quality-adjusted life-years An index of
with different numbers of items. Its objective is survival that is weighted or adjusted by the
the quantification of the results of a semi- patient’s quality of life during the survival
structured interview. This scale gives more period.
importance to somatic and behavioural
Quality of Life Enjoyment and Satisfaction
symptoms than to psychological manifestations
Questionnaire A self-administered
of depression. Low values indicate less
questionnaire to assess the degree of
depression.
enjoyment and satisfaction experienced by
Heterogeneity Differences between studies in subjects in various areas of daily functioning. It
terms of drugs or interventions used (either has 93 items.
the drugs being investigated or the drugs with
Relative risk A measure of the likelihood of a
which they are being compared, or dose),
certain event occurring in a group of people
participants, study setting or outcomes
taking one intervention versus another. A
measured. Where significant heterogeneity is
relative risk >1 means that the group is more
present, studies should not be statistically
at risk for the particular event and a relative
combined in a meta-analysis.
risk of <1 means that the group is less at risk.
Intention-to-treat analysis The practice of
The Schedule for Affective Disorders and
reporting results for all trial participants who
Schizophrenia – Change Version The SADS
entered the study, rather than just those who
scale was developed with the primary aim of
remained at the end. Failure to use an
differentiating between schizophrenia and
intention-to-treat analysis means that the trial
mood disorders. The scale makes use of
findings may not be representative of all the
collateral information and past history. The
people who entered the study.
SADS-C scale is adapted to measure change
Mania Rating Scale An 11-item scale, over time. It rates symptoms at their highest
measuring symptoms of mania. Scores increase level of severity over the previous week. Used
with symptom severity. serially, it provides a detailed record of the
individual’s progress.
Montgomery Asberg Depression Rating Scale
Developed using a 65-item comprehensive Simpson – Angus Scale This 10-item scale,
psychopathology scale to identify the 17 most with a scoring system of 0–4 for each item,
commonly occurring symptoms in primary measures drug-induced parkinsonism, a short-
depressive illness. Ratings on 10 items, with term drug-induced movement disorder. A low
higher score indicating poor outcome. score indicates low levels of parkinsonism.
Maximum score is 30.
Tardive dyskinesia Abnormal, repetitive and
Positive and Negative Syndrome Scale This involuntary movements around the mouth, face
schizophrenia scale has 30 items, each of which and extremities.
can be defined on a seven-point scoring system
varying from 1 = absent to 7 = extreme. This
scale can be divided into three subscales for continued
viii