Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with bipolar disorder experiencing an episode of acute mania
Intervention: Lithium ᵃ
Comparison: Valproate or quetiapine ᵃ
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Lithium versus valproate | ||
Efficacy: response: categorical, Young Mania Rating Scale (YMRS)/Schedule for Affective Disorders and Schizophrenia‐change (SADS‐C) decrease ≥50% by end of trial | No statistically significant difference | Moderate |
Efficacy: response: continuous, change in YMRS (Intention To Treat [ITT]‐Last Observation Carried Forward [LOCF]) from baseline to end of trial | No statistically significant difference | Very Low |
Efficacy: remission | No statistically significant difference | Moderate |
Total withdrawals | No statistically significant difference | High |
Adverse events: headache | Occurs more commonly with lithium compared with valproate (favours comparison) | GRADE assessment not performed for this outcome |
Adverse events: somnolence | Occurs more commonly with valproate compared with lithium (favours intervention) | High |
Adverse events: tremor | Occurs more commonly with lithium compared with valproate (favours comparison) | High |
Lithium versus quetiapine | ||
Efficacy: response: categorical, YMRS decrease by ≥50% by end of trial | No statistically significant difference | Very Low |
Efficacy: response: continuous, YMRS change from baseline at end of trial | No statistically significant difference | Low |
Efficacy: remission | No statistically significant difference | Low |
Total withdrawals | No statistically significant difference | Very Low |
Adverse events: dizziness | Occurs more commonly with quetiapine compared with lithium (favours intervention) | GRADE assessment not performed for this outcome |
Adverse events: weight gain | Occurs more commonly with quetiapine compared with lithium (favours intervention) | GRADE assessment not performed for this outcome |
Note ᵃ This evidence table summarises the findings for the comparison of lithium versus valproate and lithium versus quetiapine, which are all listed as primary options in this BMJ Best Practice topic, “Bipolar disorder in adults”. See the full CCA for information on other comparisons (lithium versus lamotrigine; lithium versus carbamazepine; lithium versus olanzapine; lithium versus topiramate).
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: People with bipolar I disorder, acute mania, or mixed episode with or without psychotic features ᵃ
Intervention: Aripiprazole ᵇ
Comparison: Placebo ᵇ
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mean change in Young Mania Rating Scale (YMRS) from baseline at three weeks | Favours intervention | Moderate |
Mean change in YMRS from baseline at six weeks | No statistically significant difference | GRADE assessment not performed for this outcome |
Response (≥50% decrease in total YMRS from baseline) at three weeks | Favours intervention | Moderate |
Response (≥50% decrease in total YMRS from baseline) at six weeks | Favours intervention | GRADE assessment not performed for this outcome |
Clinical Global Impression (CGI) ‐ Bipolar Version: severity (mania) scale: mean change at three weeks | Favours intervention | GRADE assessment not performed for this outcome |
Requirement for anticholinergics | Favours comparison | High |
Remission (YMRS total score ≤12) at six weeks | No statistically significant difference | GRADE assessment not performed for this outcome |
Hospitalisation at three weeks | Favours intervention | GRADE assessment not performed for this outcome |
Numbers completing double‐blind treatment | No statistically significant difference | Moderate |
Adverse effects: Abnormal Involuntary Movement Scale | No statistically significant difference | GRADE assessment not performed for this outcome |
Adverse effects: akathisia | Occurs more commonly with aripiprazole compared with placebo (favours comparison) | High |
Adverse effects: nausea | Occurs more commonly with aripiprazole compared with placebo (favours comparison) | High |
Adverse effects: extrapyramidal symptoms | Occurs more commonly with aripiprazole compared with placebo (favours comparison) | GRADE assessment not performed for this outcome |
Note The Cochrane review which underpins this Cochrane Clinical Answer (CCA) notes that moderate-quality evidence shows that aripiprazole is a more effective treatment for acute mania than placebo. However, it also notes that there is minimal evidence comparing aripiprazole with other drugs and that more direct evidence is required to properly guide clinical practice. ᵃ Most of the participants were adults. However, some outcomes include data for children and adolescents as well. People at high risk of suicide or with a substance use disorder were not included. ᵇ This evidence table summarises the findings for the comparison of aripiprazole versus placebo, which is the main comparison as stated in the Cochrane review Summary of Findings table. See the full CCA for information on other comparisons (aripiprazole versus other drug treatment).
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with acute mania
Intervention: Lithium ᵃ
Comparison: Risperidone or aripiprazole ᵃ
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Lithium versus risperidone | ||
Efficacy: response | Favours comparison | Low |
Efficacy: remission | No statistically significant difference | Low |
Total withdrawals | Favours comparison | Moderate |
Adverse events: drowsiness/somnolence | Occurs more commonly with risperidone compared with lithium (favours intervention) | Moderate |
Adverse events: diarrhoea; nausea; vomiting; frequent urination; dry mouth; abdominal pain | Occurs more commonly with lithium compared with risperidone (favours comparison) | GRADE assessment not performed for these outcomes |
Adverse events: appetite increase; weight gain | Occurs more commonly with risperidone compared with lithium (favours intervention) | GRADE assessment not performed for these outcomes |
Lithium versus aripiprazole | ||
Efficacy: response | No statistically significant difference | Moderate |
Efficacy: remission | No statistically significant difference | Moderate |
Total withdrawals | No statistically significant difference | Moderate |
Adverse events | No statistically significant difference ᵇ | See note ᵇ |
Note ᵃ This evidence table summarises the findings for the comparison of lithium versus risperidone and lithium versus aripiprazole, which are all listed as primary options in this BMJ Best Practice topic “Bipolar Disorder in Adults”. See the full Cochrane Clinical Answer (CCA) for information on other comparisons (lithium versus chlorpromazine; lithium versus haloperidol; lithium versus zuclopenthixol). ᵇ The Cochrane review which underpins this CCA assessed a number of adverse events (including vomiting, mania, diarrhoea, headache, tremor, somnolence, constipation, and weight gain) and found no statistically significant difference between lithium and aripiprazole for all adverse events. The summary of findings table in the main Cochrane review notes a GRADE rating of moderate-quality evidence for tremor and somnolence/sedation, and low-quality evidence for weight gain; the reviewers did not perform a GRADE assessment for the other adverse events.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- How does lithium compare with mood stabilizers for people with acute mania?
- In people with acute mania, how does aripiprazole affect outcomes?
- How does lithium compare with antipsychotics for people with acute mania?
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