TITLE: Quetiapine for Affective and Psychotic Spectrum Disorders and Borderline
Personality Disorder: Clinical Effectiveness
DATE:
23 March 2011
RESEARCH QUESTIONS
1.
What is the clinical effectiveness of quetiapine for adults with affective spectrum
disorders?
2.
What is the clinical effectiveness of quetiapine for adults with psychotic spectrum
disorders?
3.
What is the clinical effectiveness of quetiapine for adults with borderline personality
disorder?
KEY MESSAGE
Evidence suggests that quetiapine is clinically effective for adults with major depressive
disorder, generalized anxiety disorder, and bipolar disorder, but conclusions were not consistent
concerning effectiveness for those with obsessive-compulsive disorder; there was some
evidence of effectiveness for adults with social anxiety disorder. Evidence suggests that
quetiapine is not more clinically effective than other treatments for adults with schizoaffective
disorder, but does show effectiveness in preventing relapse, after one year, in adults with
psychosis.
METHODS
A limited literature search was conducted on key resources including PubMed, The Cochrane
Library (2011, Issue 2), University of York Centre for Reviews and Dissemination (CRD)
databases, Canadian and major international health technology agencies, as well as a focused
Internet search. Methodological filters were applied to limit retrieval to health technology
assessments, systematic reviews, meta-analyses, and randomized controlled trials. Where
possible, retrieval was limited to the human population. The search was also limited to English
Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in
Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to
provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time
allowed. Rapid responses should be considered along with other types of information and health care considerations. The
information included in this response is not intended to replace professional medical advice, nor should it be construed as a
recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality
evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for
which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation
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language documents published between January 1, 2006 and March 15, 2011. Internet links
were provided, where available.
The summary of findings was prepared from the abstracts of the relevant information. Please
note that data contained in abstracts may not always be an accurate reflection of the data
contained within the full article.
RESULTS
Rapid Response reports are organized so that the higher quality evidence is presented first.
Therefore, health technology assessment reports, systematic reviews, and meta-analyses are
presented first. These are followed by pooled studies and randomized controlled trials
The literature search identified 14 systematic reviews (SR), 10 pooled analyses, and 40
randomized controlled trials (RCTs) on the clinical effectiveness of quetiapine for adults with
affective spectrum disorders and psychotic spectrum disorders (excluding schizophrenia). No
health technology assessments were identified. No literature was identified regarding quetiapine
for adults with borderline personality disorder. Additional SRs, meta-analyses, and RCTs that
did not provide results specifically for quetiapine in the abstract (but are very likely to provide
results for quetiapine in the full report), or did not specify the indication, have been listed in the
appendix.
OVERALL SUMMARY OF FINDINGS
Affective spectrum disorders
Fourteen systematic reviews on quetiapine for the treatment of affective spectrum disorders
were identified covering the following disorders: major depressive disorder (MDD),1,7
generalized anxiety disorder (GAD),2,5 bipolar disorder (BD),4,8,10,11,14 obsessive-compulsive
disorder (OCD),6,9,12,13 and one systematic review covered GAD, OCD, and BD.3 Ten pooled
analyses on quetiapine for affective spectrum disorders were identified; one15 regarding MDD
and nine regarding bipolar disorder.16-24 Thirty-five RCTs on quetiapine for affective spectrum
disorders were identified; 10 regarding MDD,25,31,32, 39,40,44,46,48,56,59 19 regarding bipolar
disorder,26,33-36,38,42,45,50,51,52,54,55,57,58,61-64 two regarding GAD,28,53 three on OCD,30,43,49 and one on
social anxiety disorder.60 Main conclusions regarding the effectiveness of treatment are
presented.
Major depressive disorder (MDD)
one SR showed second-generation antipsychotic (including quetiapine) monotherapy
and adjunctive therapy resulted in greater efficacy for MDD treatment than placebo, but
with greater risk of weight gain1
a second SR showed quetiapine was more effective than placebo for both monotherapy
and adjunctive therapy, but induced more sedation7
one pooled analysis concluded that adjunctive quetiapine-XR (extended release) therapy
was effective in improving depressive symptoms, with early onset of action15
four RCTs found that quetiapine-XR monotherapy was effective, with rapid onset of
action25,32,40,44
the most commonly reported adverse events in RCTs were dry mouth, sedation,
somnolence, headache, and insomnia25,31,32,39,40,45,59
Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
2
three RCTs found that quetiapine as adjunctive therapy with antidepressant treatment, in
doses >150mg/day, was effective in reducing symptoms of depression31,39,59
one RCT concluded that quetiapine as adjunctive treatment with lithium was significantly
more effective than adjunctive treatment with placebo46
one RCT concluded that quetiapine as adjunctive treatment with fluoxetine showed
some improvement versus placebo as adjunctive treatment48
one RCT showed that quetiapine (400 mg/day) was effective as adjunctive treatment
with lithium (600 mg/day)56
Generalized anxiety disorder (GAD)
one SR found that augmentation with quetiapine did not significantly reduce the
Hamilton Anxiety Scale (HAM-A) scores compared with placebo, but the included trials
were small and underpowered2
a second SR showed quetiapine was effective at doses of approximately 150 mg/day,
but lead to weight gain3
a third SR concluded that monotherapy with quetiapine may be as efficacious as
antidepressant therapy in reducing symptoms, however it had lower tolerability due to
weight gain, sedation, and extrapyramidal side effects5
one RCT showed that quetiapine-XR was effective, with early onset of action28
a second RCT concluded that quetiapine as adjunctive treatment with paroxetine CR
was not more effective that adjunctive treatment with placebo53
Bipolar disorder
For both bipolar depression and mania:
two RCTs reported that quetiapine as adjunctive therapy with lithium or divalproex
resulted in significant decrease in recurrence of mood events42,54
one RCT concluded quetiapine was more effective than sodium valproate for depressive
symptoms but not more effective for manic symptoms50
one RCT stated that quetiapine showed more adverse cognitive effects and increased
somnolence compared with risperidone58
two RCTs regarding patients with bipolar disorder plus alcohol dependence concluded
adjunctive treatment with quetiapine did not affect alcohol dependence35,40
one RCT regarding patients with bipolar disorder plus cocaine or methamphetamine
dependence, showed that quetiapine was effective for depressive symptoms and
reduced drug cravings52
For bipolar depression:
several SRs showed quetiapine was effective in reducing symptoms compared with
placebo3,4,8,10
one SR stated that quetiapine showed rapid onset of action4
four pooled analyses concluded that quetiapine was effective versus placebo for bipolar
depression16,17,19,20
two pooled analyses reported that quetiapine was generally well tolerated16,17
one pooled analysis reported that common adverse events with quetiapine were dry
mouth, somnolence, sedation, dizziness, and constipation.20
several RCTs showed that quetiapine was significantly more effective in treating bipolar
depression than placebo34,36,38,55,61,64
several RCTs stated that quetiapine was generally well tolerated34,36,38,61,64
Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
3
one RCT concluded that quetiapine provided significant improvement in quality of sleep
versus placebo57
For mania:
one SR reported a significant decrease in mania was measured with quetiapine as cotherapy with a mood stabilizer versus monotherapy with a mood stabilizer11
a second SR concluded that quetiapine showed significant effectiveness as
monotherapy and adjunctive therapy14
four pooled analyses showed significant improvement of symptoms for quetiapine
compared with placebo18,21,22,23
one pooled analysis reported adverse events that were similar to those found with
quetiapine for bipolar depression18
two RCTs stated that quetiapine resulted in rapid improvement of symptoms26,51
one RCT reported that quetiapine was associated with few adverse events26
one RCT concluded that quetiapine was marginally more effective than placebo33
one RCT concluded that quetiapine as adjunctive treatment with lithium or divaproex
was not more statistically effective than adjunctive placebo, but was well tolerated62
Obsessive-compulsive disorder (OCD)
one SR concluded quetiapine was not consistently effective in doses of 300 mg/day3
two SRs showed no conclusive evidence that augmentation therapy with quetiapine was
effective6,12
two SRs reported evidence of efficacy with quetiapine as augmentation therapy9,13
one RCT concluded that quetiapine as adjunctive treatment with SSRIs (selective
serotonin reuptake inhibitor) was effective30
one RCT concluded that quetiapine as adjunctive treatment with SRIs was not effective
versus placebo49
a third RCT concluded that quetiapine as adjunctive treatment with citalopram was
significantly more effective than citalopram alone43
Social anxiety disorder (SAD)
one RCT stated that quetiapine monotherapy showed effective improvement in most of
the assessment scales versus placebo60
Psychotic spectrum disorders
Five RCTs27,29,37,41,47 regarding patients with psychotic spectrum disorders were identified; three
regarding schizoaffective disorder27,41,47 and two regarding patients with psychosis.29,37 No
health technology assessments, systematic reviews, meta-analyses, or pooled analyses were
identified. Main conclusions regarding the effectiveness of treatment are presented.
Schizoaffective disorder
quetiapine at 1200 mg/day was no more effective than a 600 mg/day dose27
second-generation antipsychotics (including quetiapine) showed moderate improvement
in cognitive test performance, but with no difference compared with haloperidol41
in mentally stable, obese, or overweight patients, switching from olanzapine to
quetiapine did not shorten the time to relapse versus remaining with olanzapine, but
treatment with quetiapine did result in more drop-outs due to adverse events47
Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
4
Psychosis
in patients with first episode psychosis who had been in treatment for one year,
maintenance with quetiapine (400 mg/day) resulted in a substantial decrease in the rate
of relapse in the second year29
quetiapine as an adjunct to venlafaxine was more effective than venlafaxine alone for
treating psychotic depression37
Borderline personality disorder
No literature on the clinical effectiveness of quetiapine for adults with borderline personality
disorder was identified.
Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
5
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PREPARED BY:
Canadian Agency for Drugs and Technologies in Health
Tel: 1-866-898-8439
www.cadth.ca
Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
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APPENDIX – FURTHER INFORMATION
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Quetiapine for the Affective and Psychotic Spectrum Disorders and Borderline Personality Disorder
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