doi: 10.1002/14651858.CD004048.pub4.
Lithium for acute mania
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- PMID: 31152444
- PMCID: PMC6544558
- DOI: 10.1002/14651858.CD004048.pub4
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Lithium for acute mania
Cochrane Database Syst Rev.
.
Abstract
Background: Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective maintenance treatment for bipolar disorder. It acts as mood stabiliser and reduces the risk of suicide. However, evidence assessing the efficacy of lithium in the treatment of acute mania is less robust. Current evidence-based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments: more definite evidence is needed to decide if lithium should be the first-line therapy.
Objectives: 1. To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2. To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.
Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO. We also searched the World Health Organization trials portal (ICTRP) and ClinicalTrials.gov. We checked the reference lists of all included studies and relevant systematic reviews. We have incorporated studies from searches to 18 May 2018 into the current analyses.
Selection criteria: Prospective randomised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania. We included anyone with bipolar disorder, male and female, of any age.
Data collection and analysis: At least two review authors independently extracted data and assessed methodological quality. We used odds ratios (ORs) to analyse binary efficacy outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuously distributed outcomes. We used a fixed-effect model unless heterogeneity was moderate or substantial, in which case we used a random-effects model. We used Review Manager 5 to analyse data. We assessed the certainty of evidence for individual outcomes using the GRADE approach.
Main results: We found 36 randomised controlled studies comparing lithium with placebo, one of 12 drugs, or electroconvulsive therapy for treatment of acute mania. Studies included male and female participants (n = 4220), of all ages, who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder.Risk of bias was variable; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on randomisation leading to an 'unclear' rating for selection bias.Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response (OR 2.13, 95% confidence interval (CI) 1.73 to 2.63; participants = 1707; studies = 6; I2 = 16%; high-certainty evidence), or remission (OR 2.16, 95% CI 1.73 to 2.69; participants = 1597; studies = 5; I2 = 21%; high-certainty evidence).Lithium was more likely than placebo to cause tremor (OR 3.25, 95% CI 2.10 to 5.04; participants = 1241; studies = 6; I2 = 0%; high-certainty evidence), and somnolence (OR 2.28, 95% CI 1.46 to 3.58; participants = 1351; studies = 7; I2 = 0%; high-certainty evidence).There was insufficient evidence to determine the effect of lithium for all-cause dropouts (OR 0.76; 95% CI 0.46 to 1.25; participants = 1353; studies = 7; I2 = 75%; moderate-certainty evidence), and weight gain (OR 1.48, 95% CI 0.56 to 3.92; participants = 735, studies = 3; I2= 51%; moderate-certainty evidence).Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response, there was only very low-certainty evidence regarding lithium compared to haloperidol (MD -2.40, 95% CI -6.31 to 1.50; participants = 80; studies = 3; I2 = 95%), quetiapine (OR 0.66, 95% CI 0.28 to 1.55; participants = 335; studies = 2; I2 = 71%), and carbamazepine (SMD 0.21, 95% CI -0.18 to 0.60; participants = 102; studies = 3; I2 = 0%).Lithium was probably less likely to induce a response than olanzapine (OR 0.44, 95% CI 0.20 to 0.94; participants = 180; studies = 2; I2 = 0%; moderate-certainty evidence).Lithium may be less likely to induce a response than risperidone (MD 7.28, 95% CI 5.22 to 9.34; participants = 241; studies = 3; I2 = 49%; low-certainty evidence).There was no evidence of a difference between lithium and valproate (OR 1.22, 95% CI 0.87 to 1.70; participants = 607; studies = 5; I2 = 22%; moderate-certainty evidence).There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania (OR 2.28, 95% CI 1.63 to 3.20; participants = 660; studies = 1).Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence.
Authors' conclusions: This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor. Limited evidence suggests little or no difference between lithium and other mood stabilisers (valproate, carbamazepine) or antipsychotics (risperidone, quetiapine, haloperidol). Olanzapine may be an exception, as it is probably slightly more effective than lithium. There is uncertain evidence that risperidone may also be more effective than lithium. Lithium is probably more effective at treating acute mania than topiramate. When compared to placebo, lithium was more likely to cause adverse events. However, when compared to other drugs, too few studies provided data on adverse effects to provide high-certainty evidence. More, rigorously designed, large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania.
Conflict of interest statement
Rebecca F McKnight: no conflicts of interest Saïk JGN de La Motte de Broöns de Vauvert: no conflicts of interest Edward Chesney: no conflicts of interest Ben H Amit: no conflicts of interest John Geddes: no conflicts of interest Andrea Cipriani: no conflicts of interest
Figures
Study flow diagram
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
'Risk of bias graph': review authors' judgements about each risk of bias item presented as percentages across all included studies
Comparison 1 Lithium vs placebo, Outcome 1 Efficacy ‐ response (categorical): YMRS/MRS decrease by =>50% at end of trial.
Comparison 1 Lithium vs placebo, Outcome 2 Efficacy ‐ response (continuous): YMRS change from baseline at end of trial.
Comparison 1 Lithium vs placebo, Outcome 3 Efficacy ‐ response (continuous): CGI change from baseline at end of trial.
Comparison 1 Lithium vs placebo, Outcome 4 Efficacy ‐ remission (categorical): YMRS < 12 at end of trial.
Comparison 1 Lithium vs placebo, Outcome 5 Acceptability: withdrawals.
Comparison 1 Lithium vs placebo, Outcome 6 Adverse event: depression.
Comparison 1 Lithium vs placebo, Outcome 7 Adverse event: mania.
Comparison 1 Lithium vs placebo, Outcome 8 Adverse event: weight gain (categorical).
Comparison 1 Lithium vs placebo, Outcome 9 Adverse event: weight gain (continuous).
Comparison 1 Lithium vs placebo, Outcome 10 Adverse event: akathisia.
Comparison 1 Lithium vs placebo, Outcome 11 Adverse event: headache.
Comparison 1 Lithium vs placebo, Outcome 12 Adverse event: somnolence.
Comparison 1 Lithium vs placebo, Outcome 13 Adverse event: dizziness.
Comparison 1 Lithium vs placebo, Outcome 14 Adverse event: insomnia.
Comparison 1 Lithium vs placebo, Outcome 15 Adverse event: diarrhoea.
Comparison 1 Lithium vs placebo, Outcome 16 Adverse event: nausea.
Comparison 1 Lithium vs placebo, Outcome 17 Adverse event: vomiting.
Comparison 1 Lithium vs placebo, Outcome 18 Adverse event: dry mouth.
Comparison 1 Lithium vs placebo, Outcome 19 Adverse event: pain.
Comparison 1 Lithium vs placebo, Outcome 20 Adverse event: EPS.
Comparison 1 Lithium vs placebo, Outcome 21 Adverse event: tremor.
Comparison 1 Lithium vs placebo, Outcome 22 Adverse event: constipation.
Comparison 1 Lithium vs placebo, Outcome 23 Adverse event: fever.
Comparison 1 Lithium vs placebo, Outcome 24 Adverse event: rash.
Comparison 1 Lithium vs placebo, Outcome 25 Efficacy ‐ response (continuous): CGI change from baseline to end of trial.
Comparison 1 Lithium vs placebo, Outcome 26 Response: YMRS decrease by ≥ 50% end of the trial.
Comparison 1 Lithium vs placebo, Outcome 27 Response: remission YMRS < 12 at end of trial.
Comparison 1 Lithium vs placebo, Outcome 28 Efficacy ‐ response (continuous): MADRS change from baseline to end of trial.
Comparison 1 Lithium vs placebo, Outcome 29 Efficacy ‐ response (continuous): MRS score change from baseline to end of trial.
Comparison 1 Lithium vs placebo, Outcome 30 Efficacy ‐ (continuous): GAS score at end of trial.
Comparison 1 Lithium vs placebo, Outcome 31 Efficacy ‐ HAMD‐31 score at end of trial.
Comparison 1 Lithium vs placebo, Outcome 32 Efficacy ‐ BPRS score at end of trial.
Comparison 1 Lithium vs placebo, Outcome 33 PANSS change from baseline to end of trial.
Comparison 1 Lithium vs placebo, Outcome 34 CGI‐BP change from baseline to end of trial.
Comparison 1 Lithium vs placebo, Outcome 35 Use of concomitant medications.
Comparison 1 Lithium vs placebo, Outcome 36 Use of sleep medications over course of trial.
Comparison 1 Lithium vs placebo, Outcome 37 Use of anticholinergic medications.
Comparison 1 Lithium vs placebo, Outcome 38 Concomitant use of analgesics/antipyretics.
Comparison 1 Lithium vs placebo, Outcome 39 Acceptability: withdrawal due to adverse events.
Comparison 2 Lithium vs valproate, Outcome 1 Efficacy ‐ response (categorical): YMRS/SADS‐C decrease ≥ 50% by end of trial.
Comparison 2 Lithium vs valproate, Outcome 2 Efficacy ‐ response (categorical, adults): YMRS/SADS‐C decrease ≥ 50% by end of trial ADULTS only.
Comparison 2 Lithium vs valproate, Outcome 3 Efficacy ‐ response (continuous): change in YMRS (ITT‐LOCF) change from baseline to end of trial.
Comparison 2 Lithium vs valproate, Outcome 4 Efficacy ‐ response (continuous): CGI‐BP change from baseline to end of trial.
Comparison 2 Lithium vs valproate, Outcome 5 Efficacy ‐ response (continuous): Change in MADRS (ITT‐LOCF) change from baseline to end of trial.
Comparison 2 Lithium vs valproate, Outcome 6 Efficacy ‐ remission (categorical): YMRS ≤ 12 and no increase in MADRS at end of trial.
Comparison 2 Lithium vs valproate, Outcome 7 Efficacy ‐ remission (categorical): YMRS ≤ 12 and a reduction of at least 2 points on the CGI‐BP at end of trial.
Comparison 2 Lithium vs valproate, Outcome 8 Adverse event: headache.
Comparison 2 Lithium vs valproate, Outcome 9 Adverse event: somnolence.
Comparison 2 Lithium vs valproate, Outcome 10 Adverse event: tremor.
Comparison 2 Lithium vs valproate, Outcome 11 Acceptability: total withdrawals.
Comparison 2 Lithium vs valproate, Outcome 12 Efficacy ‐ response (continuous): MADRS change from baseline to end of trial.
Comparison 2 Lithium vs valproate, Outcome 13 SADS‐C mania score at end of trial.
Comparison 2 Lithium vs valproate, Outcome 14 SADS‐C depression score at end of trial.
Comparison 2 Lithium vs valproate, Outcome 15 GAS score at end of trial.
Comparison 2 Lithium vs valproate, Outcome 16 CGI‐BP end of trial score.
Comparison 2 Lithium vs valproate, Outcome 17 YMRS insight score at end of trial.
Comparison 2 Lithium vs valproate, Outcome 18 BPRS score at end of trial.
Comparison 2 Lithium vs valproate, Outcome 19 Any adverse events.
Comparison 2 Lithium vs valproate, Outcome 20 Serious adverse events.
Comparison 2 Lithium vs valproate, Outcome 21 Adverse event: diarrhoea.
Comparison 2 Lithium vs valproate, Outcome 22 Adverse event: nausea.
Comparison 2 Lithium vs valproate, Outcome 23 Concomitant medication: use of lorazepam.
Comparison 2 Lithium vs valproate, Outcome 24 Concomitant medication: use of chloral hydrate (g).
Comparison 2 Lithium vs valproate, Outcome 25 Concomitant medication: use of lorazepam (g).
Comparison 2 Lithium vs valproate, Outcome 26 Concomitant medication: use of anxiolytics.
Comparison 2 Lithium vs valproate, Outcome 27 Concomitant medication: use of antidepressants.
Comparison 3 Lithium vs lamotrigine, Outcome 1 Efficacy ‐ response (continuous): change in BPRS from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 2 Efficacy ‐ response (continuous): MRS (16 item) change from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 3 Efficacy ‐ response (continuous): CGI severity change from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 4 Efficacy ‐ response (continuous): change in GAS from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 5 Acceptability.
Comparison 3 Lithium vs lamotrigine, Outcome 6 Efficacy ‐ response (continuous): change in Hamilton depression scale (HAMD 31) from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 7 Efficacy ‐ response (categorical): ≥ 50% reduction in BPRS from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 8 Efficacy ‐ response(categorical): ≥ 50% reduction in MRS from baseline to end of trial.
Comparison 3 Lithium vs lamotrigine, Outcome 9 Efficacy ‐ response (categorical): CGI scores of 1 or 2 at the end of the trial.
Comparison 3 Lithium vs lamotrigine, Outcome 10 Adverse event: vomiting.
Comparison 3 Lithium vs lamotrigine, Outcome 11 Adverse event: all mania.
Comparison 3 Lithium vs lamotrigine, Outcome 12 Adverse event: diarrhoea.
Comparison 3 Lithium vs lamotrigine, Outcome 13 Adverse event: headache.
Comparison 3 Lithium vs lamotrigine, Outcome 14 Adverse event: tremor.
Comparison 3 Lithium vs lamotrigine, Outcome 15 Adverse event: rash.
Comparison 3 Lithium vs lamotrigine, Outcome 16 Adverse event: somnolence.
Comparison 3 Lithium vs lamotrigine, Outcome 17 Adverse event: any side effects.
Comparison 3 Lithium vs lamotrigine, Outcome 18 Adverse event: any serious event.
Comparison 3 Lithium vs lamotrigine, Outcome 19 Adverse event: constipation.
Comparison 3 Lithium vs lamotrigine, Outcome 20 Adverse event: accidental injury.
Comparison 3 Lithium vs lamotrigine, Outcome 21 Adverse event: pain.
Comparison 3 Lithium vs lamotrigine, Outcome 22 Use of concomitant psychotropic medication.
Comparison 3 Lithium vs lamotrigine, Outcome 23 Mean total dose of lorazepam (g).
Comparison 4 Lithium vs carbamazepine, Outcome 1 Efficacy ‐ response (continuous): YMRS/BPRS change from baseline to end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 2 Efficacy ‐ response (continuous): CGI change from baseline to end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 3 Efficacy ‐ response (continuous): mean length of treatment in weeks.
Comparison 4 Lithium vs carbamazepine, Outcome 4 Acceptability.
Comparison 4 Lithium vs carbamazepine, Outcome 5 Changes in side effect scores from baseline to end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 6 Response rate ≥ 50% change in YMRS from baseline to end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 7 Score of CGI‐BP of 1 or 2 at end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 8 Response: CGI change of 2 or more from baseline to end of trial.
Comparison 4 Lithium vs carbamazepine, Outcome 9 HDRS 6 weeks.
Comparison 4 Lithium vs carbamazepine, Outcome 10 HDRS >11.
Comparison 4 Lithium vs carbamazepine, Outcome 11 Adverse event: serious adverse events.
Comparison 4 Lithium vs carbamazepine, Outcome 12 Adverse event: nausea.
Comparison 4 Lithium vs carbamazepine, Outcome 13 Adverse event: sedation.
Comparison 4 Lithium vs carbamazepine, Outcome 14 Adverse event: rash.
Comparison 4 Lithium vs carbamazepine, Outcome 15 Adverse event: dizziness.
Comparison 4 Lithium vs carbamazepine, Outcome 16 Adverse event: increased appetite.
Comparison 4 Lithium vs carbamazepine, Outcome 17 Adverse event: polyuria.
Comparison 4 Lithium vs carbamazepine, Outcome 18 Adverse event: diarrhoea.
Comparison 5 Lithium vs quetiapine, Outcome 1 Efficacy ‐ response (categorical): YMRS decrease by ≥ 50% by end of trial.
Comparison 5 Lithium vs quetiapine, Outcome 2 Efficacy ‐ response (continuous): YMRS/MADRS change from baseline at end of trial.
Comparison 5 Lithium vs quetiapine, Outcome 3 Efficacy ‐ remission (categorical): Decrease in YMRS ≤ 12 by end of trial.
Comparison 5 Lithium vs quetiapine, Outcome 4 Efficacy ‐ response (continuous): MADRS change from baseline.
Comparison 5 Lithium vs quetiapine, Outcome 5 Adverse event: dizziness.
Comparison 5 Lithium vs quetiapine, Outcome 6 Adverse event: diarrhoea.
Comparison 5 Lithium vs quetiapine, Outcome 7 Adverse event: weight gain.
Comparison 5 Lithium vs quetiapine, Outcome 8 Acceptability: withdrawal.
Comparison 5 Lithium vs quetiapine, Outcome 9 PANSS score change from baseline to end of trial.
Comparison 5 Lithium vs quetiapine, Outcome 10 Change in YMRS from baseline to end of trial.
Comparison 5 Lithium vs quetiapine, Outcome 11 Use of sleep medications over the whole study.
Comparison 5 Lithium vs quetiapine, Outcome 12 Use of lorazepam over the whole study.
Comparison 5 Lithium vs quetiapine, Outcome 13 Use of anticholinergics over the whole study.
Comparison 6 Lithium vs olanzapine, Outcome 1 Efficacy ‐ response (categorical): MSRS/YMRS ≥ 50% decrease in score by end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 2 Efficacy ‐ response (continuous): change in CGI baseline to end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 3 Efficacy ‐ response (continuous): CGI severity score at end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 4 Efficacy ‐ remission (categorical): YMRS ≤ 12 at end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 5 Total withdrawal.
Comparison 6 Lithium vs olanzapine, Outcome 6 Withdrawal due to lack of efficacy.
Comparison 6 Lithium vs olanzapine, Outcome 7 Withdrawal due to adverse event.
Comparison 6 Lithium vs olanzapine, Outcome 8 Change in BPRS from baseline to end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 9 Change in CGI‐BP from baseline to end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 10 Change in MADRS from baseline to end of trial.
Comparison 6 Lithium vs olanzapine, Outcome 11 Concomitant medication: benzodiazepine use.
Comparison 6 Lithium vs olanzapine, Outcome 12 Concomitant medication: mean daily dose of lorazepam.
Comparison 6 Lithium vs olanzapine, Outcome 13 Concomitant medication: anticholinergic use.
Comparison 6 Lithium vs olanzapine, Outcome 14 Adverse event: tremor.
Comparison 7 Lithium vs chlorpromazine, Outcome 1 Efficacy ‐ response (continuous): BPRS score change from baseline to end of trial.
Comparison 7 Lithium vs chlorpromazine, Outcome 2 Efficacy ‐ response (continuous): PES change from baseline to end of trial.
Comparison 7 Lithium vs chlorpromazine, Outcome 3 Efficacy ‐ response (categorical): ≥ 50% reduction on BPRS from baseline to end of trial.
Comparison 7 Lithium vs chlorpromazine, Outcome 4 Acceptability: total withdrawals.
Comparison 8 Lithium vs haloperidol, Outcome 1 Efficacy ‐ response (continuous): change in BPRS (total) from baseline to end of trial.
Comparison 8 Lithium vs haloperidol, Outcome 2 Efficacy ‐ response (continuous): CGI change from baseline to end of trial.
Comparison 8 Lithium vs haloperidol, Outcome 3 Acceptability: change in side effect scores from baseline to end of trial.
Comparison 8 Lithium vs haloperidol, Outcome 4 Total withdrawal.
Comparison 8 Lithium vs haloperidol, Outcome 5 Concomitant medication: use of orphenadrine.
Comparison 8 Lithium vs haloperidol, Outcome 6 Concomitant medication: mean total lorazepam (mg).
Comparison 9 Lithium vs zuclopenthixol, Outcome 1 Efficacy ‐ response (categorical): BMRS change ≥ 50% from baseline to end of trial.
Comparison 9 Lithium vs zuclopenthixol, Outcome 2 Total withdrawal.
Comparison 9 Lithium vs zuclopenthixol, Outcome 3 Mean dose (mg) of extra clonazepam.
Comparison 9 Lithium vs zuclopenthixol, Outcome 4 Adverse event rating scale psychic.
Comparison 9 Lithium vs zuclopenthixol, Outcome 5 Adverse event rating scale neurological.
Comparison 9 Lithium vs zuclopenthixol, Outcome 6 Adverse event rating scale autonomic.
Comparison 9 Lithium vs zuclopenthixol, Outcome 7 Adverse event rating scale other.
Comparison 10 Lithium vs risperidone, Outcome 1 Efficacy ‐ response (continuous): YMRS/MRS change at the end of the study.
Comparison 10 Lithium vs risperidone, Outcome 2 Efficacy ‐ remission (categorical): YMRS < 12/ absence of DSM‐IV mania by end of trial.
Comparison 10 Lithium vs risperidone, Outcome 3 Efficacy ‐ response (continuous): CGI change from baseline to end of trial.
Comparison 10 Lithium vs risperidone, Outcome 4 Drowsiness/ somnolence.
Comparison 10 Lithium vs risperidone, Outcome 5 Diarrhoea.
Comparison 10 Lithium vs risperidone, Outcome 6 Nausea.
Comparison 10 Lithium vs risperidone, Outcome 7 Drowsiness/ somnolence.
Comparison 10 Lithium vs risperidone, Outcome 8 Total withdrawal.
Comparison 10 Lithium vs risperidone, Outcome 9 Vomiting.
Comparison 10 Lithium vs risperidone, Outcome 10 Withdrawal due to adverse effects.
Comparison 10 Lithium vs risperidone, Outcome 11 CGI‐BP‐IM response.
Comparison 10 Lithium vs risperidone, Outcome 12 Appetite increase.
Comparison 10 Lithium vs risperidone, Outcome 13 Constipation.
Comparison 10 Lithium vs risperidone, Outcome 14 Frequent urination.
Comparison 10 Lithium vs risperidone, Outcome 15 Weight gain.
Comparison 10 Lithium vs risperidone, Outcome 16 Dry mouth.
Comparison 10 Lithium vs risperidone, Outcome 17 Abdominal Pain.
Comparison 10 Lithium vs risperidone, Outcome 18 Concomitant medication: mean total lorazepam (mg).
Comparison 10 Lithium vs risperidone, Outcome 19 Concomitant medication: use of orphenadrine.
Comparison 11 Lithium vs aripiprazole, Outcome 1 Efficacy ‐ response (continuous): YMRS change by ≥ 50% at end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 2 Efficacy ‐ response (continuous): CGI BP change from baseline to end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 3 Efficacy ‐ remission (categorical): YMRS < 12 at end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 4 PANSS change from baseline to end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 5 Total withdrawal.
Comparison 11 Lithium vs aripiprazole, Outcome 6 CGI‐BP severity of illness score change from baseline to end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 7 MADRS change from baseline to end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 8 CGI BP depression change from baseline to end of trial.
Comparison 11 Lithium vs aripiprazole, Outcome 9 Weight.
Comparison 11 Lithium vs aripiprazole, Outcome 10 Akathisia.
Comparison 11 Lithium vs aripiprazole, Outcome 11 Constipation.
Comparison 11 Lithium vs aripiprazole, Outcome 12 Headache.
Comparison 11 Lithium vs aripiprazole, Outcome 13 Nausea.
Comparison 11 Lithium vs aripiprazole, Outcome 14 Somnolence/ sedation.
Comparison 11 Lithium vs aripiprazole, Outcome 15 Tremor.
Comparison 11 Lithium vs aripiprazole, Outcome 16 EPSE.
Comparison 11 Lithium vs aripiprazole, Outcome 17 Clinically relevant (> 7%) weight gain.
Comparison 11 Lithium vs aripiprazole, Outcome 18 Simpson Angus scale EPS LOCF.
Comparison 11 Lithium vs aripiprazole, Outcome 19 BARS score.
Comparison 11 Lithium vs aripiprazole, Outcome 20 Withdrawal due to lack of efficacy.
Comparison 11 Lithium vs aripiprazole, Outcome 21 Withdrawal due to adverse events.
Comparison 11 Lithium vs aripiprazole, Outcome 22 Concomitant use of anxiolytics.
Comparison 11 Lithium vs aripiprazole, Outcome 23 Concomitant use of analgesics/antipyretics.
Comparison 11 Lithium vs aripiprazole, Outcome 24 Concomitant use of anticholinergics.
Comparison 12 Lithium vs topiramate, Outcome 1 Efficacy ‐ response (categorical): YMRS change ≥ 50% from baseline to end of trial.
Comparison 12 Lithium vs topiramate, Outcome 2 Efficacy ‐ remission (categorical): YMRS ≤ 12 at end of trial.
Comparison 12 Lithium vs topiramate, Outcome 3 Treatment emergent depression.
Comparison 12 Lithium vs topiramate, Outcome 4 DSM‐IV responders at day 21.
Comparison 12 Lithium vs topiramate, Outcome 5 Mania exacerbation ≥ YMRS 10%.
Comparison 12 Lithium vs topiramate, Outcome 6 Suicidal ideation.
Comparison 12 Lithium vs topiramate, Outcome 7 Suicide attempt.
Comparison 13 Lithium vs clonazepam, Outcome 1 Efficacy ‐ response (continuous): change in CGI score from baseline to end of study.
Comparison 13 Lithium vs clonazepam, Outcome 2 Efficacy ‐ response (continuous): change in CGI score from baseline to end of study [double blind only].
Comparison 13 Lithium vs clonazepam, Outcome 3 Change in mania rating from baseline to end of trial.
Comparison 13 Lithium vs clonazepam, Outcome 4 Change in BPRS from baseline to end of trial.
Comparison 13 Lithium vs clonazepam, Outcome 5 Change in IMPS from baseline to end of trial.
Comparison 13 Lithium vs clonazepam, Outcome 6 Change in GAF from baseline to end of trial.
Comparison 13 Lithium vs clonazepam, Outcome 7 Simpson Angus scale change from baseline to end of trial.
Comparison 13 Lithium vs clonazepam, Outcome 8 Use of rescue medications (haloperidol).
Comparison 14 Lithium vs ECT, Outcome 1 Efficacy ‐ response (continuous): MRS mean change from baseline to end of trial.
Comparison 14 Lithium vs ECT, Outcome 2 Efficacy ‐ response (continuous): BPRS mean change from baseline to end of trial.
Comparison 14 Lithium vs ECT, Outcome 3 Efficacy ‐ response (continuous): CGI mean change from baseline to end of trial.
Comparison 14 Lithium vs ECT, Outcome 4 Efficacy ‐ response (continuous): GAS mean change from baseline to end of trial.
Comparison 14 Lithium vs ECT, Outcome 5 Efficacy ‐ response (continuous): Hamilton Depression Scale mean change from baseline to end of trial.
Comparison 15 Lithium vs all antimanic agents, Outcome 1 Efficacy ‐ response (categorical): YMRS/MRS/BPRS change by ≥ 50% at end of trial.
Comparison 15 Lithium vs all antimanic agents, Outcome 2 Efficacy ‐ response (continuous): YMRS/BPRS change from baseline to end of trial.
Comparison 15 Lithium vs all antimanic agents, Outcome 3 Acceptability ‐ total withdrawals.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 1 Clinically significant increases in TSH.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 2 Any serious adverse event.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 3 Attempted suicide.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 4 Accidental injury.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 5 Any adverse event.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 6 Anorexia.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 7 Infection.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 8 Weight loss.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 9 Agitation.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 10 Back pain.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 11 Convulsions.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 12 Dyspepsia.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 13 AIMS score.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 14 Emotional lability.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 15 Influenza.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 16 Psychotic disorder.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 17 Suicidal ideation.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 18 Simpson Angus scale EPS LOCF.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 19 Motor dysfunction.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 20 Leukopenia.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 21 Aggression/ hostility.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 22 BARS score.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 23 Gastroenteritis.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 24 Increased appetite.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 25 Hyperprolactinaemia > 20 mcg for men and > 30 mcg in women.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 26 Change in thyrotropin in mIU/L.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 27 Arthralgia.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 28 Dysarthria.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 29 Twitching.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 30 Exacerbation of cough.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 31 Rhinitis.
Comparison 16 Appendix 1: lithium vs placebo ‐ single trial data and less common adverse events, Outcome 32 Pruritus.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 1 Change in weight (in kg).
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 2 Weight gain greater than 7%.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 3 Change in aspartate aminotransferase IU/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 4 Change in alanine aminotransferase IU/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 5 Change in platelet count (x10^9/L).
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 6 Fatigue.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 7 Constipation.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 8 Change in creatinine mcmol/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 9 Thyroid function.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 10 Change in glucose in mmol/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 11 Change in cholesterol in mmol/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 12 Change in triglycerides in mmol/L.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 13 Somnolence.
Comparison 17 Appendix 2: lithium vs valproate ‐ single trial data and less common adverse events, Outcome 14 Constipation.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 1 Clinically significant increases in TSH.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 2 Dry mouth.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 3 Somnolence.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 4 Akathisia.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 5 Insomnia.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 6 URTI.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 7 Headache.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 8 EPS.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 9 ECG changes.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 10 Asthenia.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 11 Constipation.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 12 Depression.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 13 Cardiac disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 14 Weight loss.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 15 Anorexia.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 16 Bone marrow depression.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 17 Nausea.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 18 Raised neutrophils > 10x109 /L.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 19 Deranged LFTs > 3x normal range.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 20 Vomiting.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 21 High blood glucose.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 22 Hyperprolactinaemia > 20mcg for men and > 30mcg in women.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 23 GI disorder.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 24 Nervous system disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 25 Infections and infestations.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 26 Tremor.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 27 Respiratory, thoracic and mediastinal disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 28 Skin and subcutaneous tissue disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 29 Eye disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 30 Psychiatric disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 31 Metabolism and nutritional disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 32 MSK and connective tissue disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 33 Renal and urinary disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 34 Reproductive system and breast disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 35 Vascular disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 36 Blood and lymphatic disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 37 Hepatobiliary disorders.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 38 Injury, poisoning and procedural complications.
Comparison 18 Appendix 3: lithium vs quetiapine ‐ single trial data and less common adverse events, Outcome 39 Weight gain.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 1 Convulsions.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 2 Insomnia.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 3 EPS.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 4 Dry Mouth.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 5 Infection.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 6 Nausea.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 7 Akathisia.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 8 Dyspepsia.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 9 Agitation.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 10 Emotional lability.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 11 Influenza.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 12 Psychotic disorder.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 13 Motor dysfunction.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 14 Dizziness.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 15 Syncope.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 16 Depression.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 17 Arthralgia.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 18 Back pain.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 19 Exacerbation of cough.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 20 Rhinitis.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 21 Pruritus.
Comparison 19 Appendix 4: lithium vs lamotrigine ‐ single trial data and less common adverse events, Outcome 22 Non fatal serious adverse events.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 1 Tremor.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 2 Any adverse event.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 3 Nausea.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 4 Constipation.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 5 Nasopharyngitis.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 6 Somnolence.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 7 Vomiting.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 8 Diarrhoea.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 9 Dizziness.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 10 Cough.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 11 Restlessness.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 12 Tachycardia.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 13 Fatigue.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 14 Headache.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 15 Increased appetite.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 16 Tonsillitis.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 17 URTI.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 18 Dry Mouth.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 19 Gingivitis.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 20 Haemorrhoids.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 21 Adverse effects possibly related to drug use.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 22 Metabolism and nutrition disorders.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 23 Nervous system disorders.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 24 Abnormal hepatic function.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 25 EPSE.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 26 Significant high cholesterol.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 27 Significant high glucose.
Comparison 20 Appendix 5: lithium vs olanzapine ‐ single trial data and less common adverse events, Outcome 28 Weight gain > 7%.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 1 ≥ 50% change in YMRS.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 2 YMRS ≤ 12.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 3 Tremor.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 4 Adverse events.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 5 Dizziness.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 6 Dyspepsia.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 7 EPSE.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 8 Proportion of patients requiring seclusion.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 9 AIMS score.
Comparison 21 Appendix 6: lithium vs risperidone ‐ single trial studies and less common adverse events, Outcome 10 YMRS change from baseline at week 3.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 1 Toxicity.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 2 Intercurrent illness.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 3 Side effects total: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 4 Side effects total: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 5 Anorexia: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 6 Anorexia: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 7 Nausea: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 8 Nausea: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 9 Vomiting: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 10 Vomiting: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 11 Diarrhoea: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 12 Dry mouth: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 13 Dry mouth: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 14 Constipation: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 15 Constipation: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 16 Abdominal pain: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 17 Muscle weakness: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 18 Ataxia: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 19 Tremor: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 20 Tremor: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 21 Facial twitching; highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 22 Parkinsonism: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 23 Somnolence: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 24 Somnolence; highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 25 Confusion: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 26 Confusion: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 27 Slurred speech: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 28 Slurred speech: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 29 Blurred vision: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 30 Dizziness: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 31 Dizziness: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 32 Seizures: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 33 Hypotensive reaction: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 34 Hypotensive reaction: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 35 Pruritus: highly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 36 Polyuria: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 37 Severe reaction: mildly active group.
Comparison 22 Appendix 7: lithium vs chlorpromazine ‐ adverse events, Outcome 38 Severe reaction: highly active group.
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Lerer 1987 {published data only}
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NCT01166425 {published data only}
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References to studies awaiting assessment
Grunze 2006 {published and unpublished data}
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Itoh 1974 {published data only}
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Maggs 1963 {published data only}
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NCT00183443 {published data only}
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NCT00893581 {published data only}
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- DelBello M, Duran L, Strawn J, Klein C, Welge J, Blom T, et al. Neural markers of treatment effects and response in youth with first‐episode mania [64th Annual Meeting American Academy of Child and Adolescent Psychiatry, AACAP 2017]. Journal of the American Academy of Child and Adolescent Psychiatry 2017;56(10):S137.
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References to ongoing studies
NCT01893229 {unpublished data only}
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