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Research · Medication

Atypical antipsychotics

Meta-analyses found antipsychotics raised response in acute schizophrenia to 51% against 30% on placebo and cut one-year relapse from 64% to 27%. Added to an antidepressant, quetiapine and aripiprazole raised remission. Weight gain, sleepiness and restlessness were frequent. Labels carry boxed warnings for higher death rates in older people with dementia and for suicidal thoughts in young people.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Quetiapine is FDA-approved for schizophrenia, manic episodes of bipolar I disorder and depressive episodes of bipolar disorder, and its extended-release form also as an add-on to antidepressants in major depressive disorder. Aripiprazole is FDA-approved for schizophrenia, manic and mixed episodes of bipolar I disorder, as an add-on in major depressive disorder, for irritability associated with autistic disorder and for Tourette's disorder. Neither is approved for insomnia, anxiety or dementia-related psychosis.
Also called
quetiapine, Seroquel, Seroquel XR, aripiprazole, Abilify, second-generation antipsychotics, atypical neuroleptics
Taken for
schizophrenia, bipolar disorder, mania, bipolar depression, depression not helped by an antidepressant, sleep, insomnia, anxiety, agitation in dementia, irritability in autism, tics

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help10

Reported risks20

What people take it for, and what was found

Shown to help10

StrongVery common

Schizophrenia, acute symptoms

Shown to bring at least a minimal response in 51% of people with acute schizophrenia against 30% on placebo, with a higher response threshold met by 23% against 14%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 167 placebo-controlled trials of antipsychotics, the standardized mean difference for overall efficacy was 0.47 (95% credible interval 0.42 to 0.51), falling to 0.38 after accounting for small-trial effects and publication bias. At least a minimal response occurred in 51% against 30% on placebo, and the authors' higher response threshold was met by 23% against 14%. Positive symptoms improved more than negative symptoms or depression [1]. In a network meta-analysis of 32 oral antipsychotics, all reduced overall symptoms more than placebo, with standardized mean differences from -0.89 for clozapine to -0.03 for levomepromazine [2]. The quetiapine label reports that efficacy was established in three 6-week trials in adults and one in adolescents [3].
Population
28,102 mainly chronic participants in 167 trials [1]; 53,463 participants in 402 studies [2].
Sources
[1], [2], [3]
Caveats
These are class results across many antipsychotics, and the abstracts do not give the figures for quetiapine or aripiprazole alone. Only a minority met the higher response threshold. Industry sponsorship was associated with smaller effect sizes [1].
ModerateVery common

Schizophrenia, preventing relapse

Shown to cut relapse within a year to 27% on an antipsychotic against 64% on placebo in people with schizophrenia, about 1 fewer relapse per 3 treated.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 65 trials, relapse at one year occurred in 27% on antipsychotic drugs and 64% on placebo (RR 0.40, 95% CI 0.33 to 0.49, number needed to treat 3). Readmission occurred in 10% against 26% (number needed to treat 5). More people on the drugs gained weight (10% against 6%), had movement disorders (16% against 9%) and had sedation (13% against 9%) [4].
Population
6,493 patients in 65 trials [4].
Sources
[4], [3]
Caveats
A class result covering first- and second-generation drugs, with substantial heterogeneity in effect size. The quetiapine label states that its maintenance use in schizophrenia has not been systematically evaluated in controlled trials [3].
Moderate

Bipolar mania

Shown to reduce mania symptoms more than placebo for both quetiapine and aripiprazole, by a standardized mean difference of 0.37, and less than haloperidol.

The numbers and sources
Effect
In a network meta-analysis of drugs for acute mania, quetiapine (SMD -0.37, 95% CI -0.51 to -0.23) and aripiprazole (SMD -0.37, 95% CI -0.51 to -0.23) each reduced mania symptoms more than placebo. Haloperidol (SMD -0.56) reduced symptoms more than either. Quetiapine led to fewer discontinuations than placebo or lithium [5].
Population
Randomized trials of antimanic drugs in adults with acute mania [5].
Sources
[5]
Caveats
One network meta-analysis of short trials. The abstract read here does not give the number of trials or participants.
Moderate

Bipolar depression

Shown to reduce depressive symptoms in bipolar depression more than placebo on quetiapine 150 or 300 mg a day, without a clear gain in response or remission rates.

The numbers and sources
Effect
In a network meta-analysis of 103 trials, extended-release quetiapine 150 and 300 mg a day was among the treatments that outperformed placebo for depressive symptoms once the analysis was limited to low-risk-of-bias studies. No treatment outperformed placebo for response, remission, acceptability or tolerability [6]. Quetiapine is approved for depressive episodes of bipolar disorder on the basis of 8-week trials [3].
Population
20,941 participants in 103 trials of 71 treatment combinations [6]; 698 people on quetiapine and 347 on placebo in the 8-week label trials [3].
Sources
[6], [3]
Caveats
The evidence is for quetiapine. Aripiprazole is not approved for bipolar depression. The abstract gives a range of estimates across drugs and no figure for quetiapine alone.
StrongVery common

Depression, added to an antidepressant

Shown to about double the odds of remission when added to an antidepressant in depression that had not responded, with about 1 extra remission per 9 treated.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 16 trials, adding an atypical antipsychotic raised response (OR 1.69, 95% CI 1.46 to 1.95) and remission (OR 2.00, 95% CI 1.69 to 2.37) against placebo, and people stopped for adverse events more often (OR 3.91, 95% CI 2.68 to 5.72) [8]. A second meta-analysis found remission odds ratios of 2.01 for aripiprazole (95% CI 1.48 to 2.73) and 1.79 for quetiapine (95% CI 1.33 to 2.42), each with a number needed to treat of 9. Effects on clinician-rated depression severity were small to moderate (Hedges' g 0.26 to 0.48) [9].
Population
3,480 patients in 16 trials [8]; adults with treatment-resistant depression in 14 trials of 4 to 12 weeks [9].
Sources
[8], [9]
Caveats
Short trials of 4 to 12 weeks. The band above is the share gaining remission beyond placebo, about 1 in 9. In the aripiprazole add-on trials, restlessness affected 25% against 4% on placebo [10].
Strong

Generalized anxiety

Shown to lower generalized anxiety scores by 3.6 points more than placebo on quetiapine, the largest effect in a network meta-analysis, with more dropouts than placebo.

The numbers and sources
Effect
In a network meta-analysis of 89 trials, quetiapine lowered Hamilton anxiety scores by 3.60 points more than placebo (95% credible interval 2.39 to 4.83), the largest effect of 22 drugs, and was poorly tolerated against placebo (OR 1.44, 95% credible interval 1.16 to 1.80) [11]. A pooled analysis of 3 trials found quetiapine gave a 26% greater likelihood of at least 50% improvement on the same scale than placebo [12].
Population
25,441 patients in 89 trials [11]; 3 quetiapine trials within a review of 162 off-label trials [12].
Sources
[11], [12]
Caveats
Not an approved use. The evidence is for quetiapine. Adverse events were common [12].
Moderate

Sleep, low-dose quetiapine

Shown to improve sleep quality and add about 48 minutes of sleep against placebo, mostly in people with anxiety or depression, with frequent side effects.

The numbers and sources
Effect
In a meta-analysis of 21 trials, quetiapine improved sleep quality against placebo (SMD -0.57, 95% CI -0.75 to -0.40), with significant effects in the generalized anxiety, major depression and healthy subgroups and at 50, 150 and 300 mg. Total sleep time rose by 47.91 minutes against placebo (95% CI 28.06 to 67.76) and did not differ from other psychiatric drugs (-4.19 minutes, 95% CI -19.43 to 11.05). Adverse events and discontinuation because of them were common [13].
Population
21 clinical trials, mainly in people with generalized anxiety disorder or major depressive disorder and in healthy volunteers [13].
Sources
[13]
Caveats
Not an approved use. Most trials measured sleep as a secondary outcome in people treated for another condition, and results in older people were highly heterogeneous. See the block on low-dose quetiapine and cardiovascular events below.
Moderate

Agitation and psychosis in dementia

Shown to produce small improvements in behavioral symptoms of dementia on aripiprazole, with effect sizes of 0.12 to 0.20, against a higher death rate than placebo.

The numbers and sources
Effect
Among 14 placebo-controlled trials in older people with dementia, small but statistically significant effect sizes of 0.12 to 0.20 on global behavioral symptom scores were seen for aripiprazole, olanzapine and risperidone. In older people, adverse events included an increased risk of death, with one extra death per 87 treated [12].
Population
Older people with dementia in 14 placebo-controlled trials [12].
Sources
[12]
Caveats
Not an approved use, and both labels carry a boxed warning about it. The review's summary names aripiprazole, olanzapine and risperidone as showing benefit, not quetiapine.
ModerateStudied in children

Irritability in autism

Shown to lower irritability scores by about 6 points more than placebo on aripiprazole in children and adolescents with autism over 8 weeks.

The numbers and sources
Effect
In two 8-week trials, aripiprazole improved the irritability subscale of the Aberrant Behavior Checklist by 6.17 points more than placebo (95% CI 3.26 to 9.07), hyperactivity by 7.93 points and stereotypy by 2.66 points. Weight rose by a mean of 1.13 kg more than placebo (95% CI 0.71 to 1.54) [14].
Population
308 children and adolescents with autism spectrum disorder in two trials [14].
Sources
[14]
Caveats
The evidence is for aripiprazole, rated moderate quality, in children and adolescents only.
Limited

Tics in Tourette's disorder

The label reports that aripiprazole reduced tic scores more than placebo in two trials of 8 and 10 weeks in patients aged 6 to 18.

The numbers and sources
Effect
The aripiprazole label states that efficacy in Tourette's disorder was established in two placebo-controlled trials, with change in a total tic score as the primary outcome. More than 65% of participants were under 13 [10].
Population
Patients aged 6 to 18 with Tourette's disorder and a total tic score of at least 20 to 22 out of 50 [10].
Sources
[10]
Caveats
The evidence is for aripiprazole. Effect sizes were not read from the label for this page, and no meta-analysis was sourced.

Mixed results1

Moderate

Bipolar disorder, preventing new episodes

Mixed results: most maintenance drugs lowered relapse against placebo in a network meta-analysis, while the estimate for aripiprazole did not reach significance.

The numbers and sources
Effect
In a network meta-analysis of 33 trials of 17 maintenance treatments, all lowered the risk of any mood relapse or recurrence against placebo except aripiprazole (RR 0.62, 95% credible interval 0.38 to 1.03), carbamazepine, imipramine and paliperidone [7]. The quetiapine label describes maintenance use at 400 to 800 mg a day as an add-on to lithium or divalproex [3].
Population
6,846 participants in 33 trials published from 1970 to 2012 [7].
Sources
[7], [3]
Caveats
The abstract does not give the estimate for quetiapine. The authors judged the supporting evidence strongest for lithium.

Doses studied

The quetiapine label gives 150 to 750 mg a day for schizophrenia in adults, reached by stepwise increases from 25 mg twice a day, 300 mg once a day at bedtime for bipolar depression, and 400 to 800 mg a day as maintenance alongside lithium or divalproex [3]. The aripiprazole label gives 10 or 15 mg a day for schizophrenia, studied across 10 to 30 mg a day, and 2 to 5 mg a day to start as an add-on in depression, within a range of 2 to 15 mg a day [10].

The sleep meta-analysis found effects at 50, 150 and 300 mg of quetiapine [13]. The bipolar depression analysis covered extended-release quetiapine 150 and 300 mg a day [6]. The label trials of quetiapine in schizophrenia and mania used 75 to 800 mg a day [3].

Risks

Reported risks19

StrongVery common

Weight gain

Shown to cause a gain of 7% or more of body weight in 23% on quetiapine against 6% on placebo in schizophrenia trials, and in 8% against 3% on aripiprazole.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
A gain of 7% or more of body weight occurred on quetiapine in 23% against 6% on placebo in schizophrenia trials of up to 6 weeks, 21% against 7% in mania trials and 8% against 2% in bipolar depression trials [3]. On aripiprazole it occurred in 8.1% against 3.2% in schizophrenia trials, 2.2% against 2.7% in mania trials and 5.2% against 0.6% as an add-on in depression, where mean weight rose 1.7 kg against 0.4 kg [10]. Across 18 antipsychotics, mean weight change against placebo over a median 6 weeks ranged from -0.23 kg for haloperidol to 3.01 kg for clozapine [16].
Population
391 people on quetiapine and 206 on placebo in schizophrenia trials [3]; 852 on aripiprazole and 379 on placebo in schizophrenia trials [10]; 25,952 patients in 100 trials [16].
Sources
[3], [10], [16]
Caveats
Short trials. In mania trials, weight gain on aripiprazole did not exceed placebo. The network meta-analysis abstract gives the range across drugs and not the figures for these two.
StrongVery common

Sleepiness

Shown to cause sleepiness in 57% on quetiapine against 15% on placebo in bipolar depression trials, and in 18% against 11% in schizophrenia trials.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
On quetiapine, somnolence was reported by 57% against 15% on placebo in bipolar depression trials, 18% against 11% in schizophrenia trials, 16% against 4% in mania trials and 34% against 9% when added to lithium or divalproex for mania [3]. On aripiprazole, sedation was reported by 7% against 4% in one pooled adult table and 8% against 3% in another [10]. In maintenance trials across antipsychotics, sedation affected 13% against 9% on placebo [4].
Population
698 people on quetiapine and 347 on placebo in bipolar depression trials, and 510 and 206 in schizophrenia trials [3]; adults in aripiprazole label trials [10]; 6,493 patients in 65 trials [4].
Sources
[3], [10], [4]
Caveats
Sleepiness was far more frequent on quetiapine than on aripiprazole in these label tables, which come from separate trials and were not compared head to head.
StrongVery common

Restlessness and movement side effects

Shown to cause restlessness in 25% on aripiprazole against 4% on placebo when added to an antidepressant, and in 8% against 4% in schizophrenia trials.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
On aripiprazole, akathisia-related events were reported by 25% against 4% on placebo as an add-on in depression, and by 8% against 4% in adult schizophrenia trials. Other movement events occurred in 13% against 12% in schizophrenia trials [10]. On quetiapine in bipolar depression trials, akathisia was reported by 4% against 1% and extrapyramidal disorder by 3% against 1% [3]. In maintenance trials across antipsychotics, movement disorders affected 16% against 9% on placebo [4]. A review of off-label use named akathisia as an adverse event of aripiprazole in adults under 65 [12].
Population
Adults in aripiprazole and quetiapine label trials [10][3]; 6,493 patients in 65 trials [4].
Sources
[10], [3], [4], [12]
Caveats
The band above is the akathisia rate on aripiprazole as an add-on in depression. Rates on quetiapine were lower.
ModerateVery common

Tardive dyskinesia

Linked to tardive dyskinesia in 20.7% of people on second-generation antipsychotics across studies, against 30.0% on first-generation drugs and 7.2% with no earlier first-generation exposure.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 41 studies, the prevalence of tardive dyskinesia was 20.7% during current second-generation treatment (95% CI 16.6 to 25.4) and 30.0% during first-generation treatment (95% CI 26.4 to 33.8). In four studies of people never exposed to first-generation drugs, it was 7.2% [18]. Both labels warn that this syndrome of involuntary movements may be irreversible [3][10].
Population
11,493 people in 41 studies, mean age 42.8, 77% with schizophrenia-spectrum disorders [18].
Sources
[18], [3], [10]
Caveats
Prevalence in people treated long term, mostly for schizophrenia, with no placebo group. Many on second-generation drugs had earlier first-generation exposure, and prevalence rose with age and length of illness.
ModerateVery common

Dry mouth, constipation and dizziness

Shown to cause dry mouth in 44% on quetiapine against 13% on placebo in bipolar depression trials, with constipation and dizziness also more frequent.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In 8-week bipolar depression trials of quetiapine: dry mouth 44% vs 13% on placebo, dizziness 18% vs 7%, constipation 10% vs 4% and fatigue 10% vs 8%. In schizophrenia and mania trials: dry mouth 9% vs 3%, constipation 8% vs 3%, dizziness 11% vs 5% and tachycardia 6% vs 4% [3].
Population
698 people on quetiapine and 347 on placebo in bipolar depression trials, and 719 and 404 in schizophrenia and mania trials [3].
Sources
[3]
Caveats
The evidence is for quetiapine.
ModerateVery common

Symptoms after stopping

Shown to cause one or more discontinuation symptoms in 12.1% after abruptly stopping extended-release quetiapine, against 6.7% after stopping placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In short-term trials with a discontinuation phase, one or more symptoms after abrupt stopping were reported by 12.1% (241 of 1,993) on extended-release quetiapine and 6.7% (71 of 1,065) on placebo. The label names insomnia, nausea and vomiting as acute withdrawal symptoms described after abrupt cessation of atypical antipsychotics [3].
Population
1,993 people stopping extended-release quetiapine and 1,065 stopping placebo [3].
Sources
[3]
Caveats
The evidence is for quetiapine after short-term use. No study of misuse or dependence was sourced for this page.
ModerateCommon

FDA boxed warning: suicidal thoughts and behaviors in young people

FDA states antidepressants raised suicidal thoughts and behaviors in children, adolescents and young adults in short trials, 14 more cases per 1,000 under age 18.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Both labels carry the antidepressant class boxed warning because the drugs are used in depression. In FDA's pooled analyses of placebo-controlled antidepressant trials, the difference from placebo in cases of suicidal thoughts or behaviors per 1,000 patients treated was 14 more under age 18, 5 more at ages 18 to 24, 1 fewer at ages 25 to 64 and 6 fewer at 65 and older. No suicides occurred in the pediatric trials [3][10].
Population
Placebo-controlled trials of antidepressants pooled by FDA [3].
Sources
[3], [10]
Caveats
The pooled analyses are of antidepressants as a group, not of quetiapine or aripiprazole. The label reports differences from placebo, not absolute rates, so the band above is the excess under age 18.
ModerateCommon

Blood sugar and cholesterol

Shown to raise fasting blood sugar to diabetic levels in 2.4% on quetiapine against 1.4% on placebo in trials of up to 12 weeks.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In short-term trials, fasting glucose shifted from normal to 126 mg/dL or above in 2.4% of 2,907 people on quetiapine and 1.4% of 1,346 on placebo. The label states that hyperglycemia, in some cases with ketoacidosis, coma or death, has been reported with atypical antipsychotics [3]. Across 18 antipsychotics, changes against placebo ranged from -0.29 to 1.05 mmol/L for glucose, -0.09 to 0.56 mmol/L for total cholesterol and -0.01 to 0.98 mmol/L for triglycerides, with clozapine and olanzapine at the high end [16]. At low doses, new type 2 diabetes was not more frequent on quetiapine than on SSRIs in a matched cohort (incidence rate ratio 0.99, 95% CI 0.87 to 1.13) [17].
Population
4,253 adults in quetiapine trials of up to 12 weeks [3]; 25,952 patients in 100 trials [16]; 54,616 matched pairs starting low-dose quetiapine or an SSRI in Denmark [17].
Sources
[3], [16], [17]
Caveats
The glucose figure is for quetiapine. The low-dose cohort is observational and compared quetiapine with another drug class.
ModerateCommon

Low blood pressure on standing and fainting

Shown to cause fainting in 1% on quetiapine against 0.2% on placebo, and low blood pressure on standing in 4% against 1%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Syncope was reported in 1% (28 of 3,265) on quetiapine and 0.2% (2 of 954) on placebo, postural hypotension in 4% against 1% in schizophrenia and mania trials, and dizziness in 11% against 5% [3]. On aripiprazole, orthostatic hypotension was reported in 1% against 0.3% and syncope in 0.5% against 0.4% [10]. Both labels state that the drug may add to the effect of blood pressure medicines [3][10].
Population
3,265 people on quetiapine across trials [3]; 2,467 adults on oral aripiprazole in short-term trials [10].
Sources
[3], [10]
Caveats
The label states that these effects occur mostly during the first dose increases on quetiapine.
ModerateCommon

Raised liver enzymes on quetiapine

Shown to raise the liver enzyme ALT in 5% on quetiapine against 1% on placebo in schizophrenia and mania trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In trials of 3 to 12 weeks, increased ALT was reported in 5% on quetiapine and 1% on placebo, and increased AST in 3% against 1% [3].
Population
719 people on quetiapine and 404 on placebo [3].
Sources
[3]
Caveats
Reported as adverse reactions in short trials, with no data here on how long the rises lasted. The evidence is for quetiapine.
LimitedHow often is not known

QT interval and sudden cardiac death

Linked to about twice the rate of sudden cardiac death in current users of atypical antipsychotics against non-users in one large cohort, rising with dose.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Current users of atypical antipsychotics had more sudden cardiac death than non-users (adjusted incidence-rate ratio 2.26, 95% CI 1.88 to 2.72), similar to users of typical antipsychotics (1.99), rising from 1.59 at low doses to 2.86 at high doses. Former users had no significant increase [19]. The quetiapine label states that trials showed no persistent increase in QT interval, that postmarketing cases of QT prolongation occurred in overdose, with other illness, or with drugs that affect electrolytes or the QT interval, and names antiarrhythmics, other antipsychotics and the antibiotics gatifloxacin and moxifloxacin as combinations to avoid [3]. Across 32 antipsychotics, QTc change against placebo ranged from -2.21 ms to 23.90 ms [2].
Population
A cohort of current, former and non-users of antipsychotics [19]; 15,467 participants in the QTc analysis [2].
Sources
[19], [3], [2]
Caveats
Observational, and a class finding. The abstract gives rate ratios without an absolute rate, and the QTc range does not single out quetiapine or aripiprazole.
LimitedHow often is not known

Low-dose quetiapine and cardiovascular events

Linked to more heart attacks, strokes and cardiovascular deaths on low-dose quetiapine than on Z-drug sleep medicines in one Danish cohort.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Compared with new users of Z-drug hypnotics, new users of low-dose quetiapine had more major adverse cardiovascular events (adjusted HR 1.13, 95% CI 1.02 to 1.24 by intention to treat, and 1.52, 95% CI 1.35 to 1.70 while on treatment), more non-fatal ischemic stroke (HR 1.37, 95% CI 1.13 to 1.68) and more cardiovascular death (HR 1.90, 95% CI 1.64 to 2.19). Results were similar against SSRIs (HR 1.42) [20].
Population
60,566 low-dose quetiapine users and 454,567 Z-drug users aged 18 to 85 in Denmark, without severe mental illness or earlier heart attack or stroke [20].
Sources
[20]
Caveats
One observational cohort comparing two drugs, with possible unmeasured differences between the people prescribed each. No absolute rates are given in the abstract.
LimitedHow often is not known

Stroke in older people with dementia

The label reports more strokes and transient ischemic attacks, some fatal, on aripiprazole than placebo in trials of older people with dementia. It gives no rate here.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In three placebo-controlled trials in dementia-related psychosis, mean age 84, cerebrovascular adverse events were more frequent on aripiprazole than placebo, with a significant dose-response relationship in the fixed-dose trial [10]. The quetiapine label reports the same finding for risperidone, aripiprazole and olanzapine in older people with dementia [3].
Population
Older people with dementia-related psychosis in three aripiprazole trials [10].
Sources
[10], [3]
Caveats
The label passage read for this page gives no percentages. The evidence is for aripiprazole and two other drugs, not quetiapine.
ModerateHow often is not known

Lower thyroid hormone on quetiapine

Shown to lower thyroid hormone levels in a dose-related way on quetiapine, with thyroxine about 20% lower at the higher end of the dose range.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label reports dose-related decreases in thyroid hormone in quetiapine trials. Total and free thyroxine fell by about 20% at the higher end of the dose range, reached a maximum in the first six weeks and reversed in nearly all cases after stopping [3].
Population
Adults in quetiapine clinical trials [3].
Sources
[3]
Caveats
An average change in a blood level. The passage read for this page gives no count of people who became hypothyroid. The evidence is for quetiapine.
LimitedHow often is not known

Compulsive urges on aripiprazole

Case reports: the label describes intense urges, particularly for gambling, and also for sex, shopping and binge eating, in people taking aripiprazole. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The aripiprazole label states that postmarketing case reports suggest people can experience intense urges, particularly for gambling, and an inability to control them. Compulsive sexual urges, shopping, and binge or compulsive eating were reported less often [10].
Population
Postmarketing case reports [10].
Sources
[10]
Caveats
Reports with no denominator. The evidence is for aripiprazole.
LimitedHow often is not known

Neuroleptic malignant syndrome

The label warns of neuroleptic malignant syndrome, a potentially fatal reaction reported with antipsychotic drugs including quetiapine. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The quetiapine label states that a potentially fatal symptom complex called neuroleptic malignant syndrome has been reported with antipsychotic drugs, and that rare cases have been reported with quetiapine [3].
Population
Reports summarized in labeling [3].
Sources
[3]
Caveats
The label says "rare" without a frequency, so no band can be set.
LimitedHow often is not known

Alcohol and sedating drugs

The label reports quetiapine strengthened the cognitive and motor effects of alcohol in a trial, and that sedation was greater when aripiprazole was combined with lorazepam.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in people with psychotic disorders, and the label urges caution with other centrally acting drugs [3]. With aripiprazole and the benzodiazepine lorazepam together, the intensity of sedation was greater than with aripiprazole alone [10].
Population
Interaction studies summarized in labeling without counts [3][10].
Sources
[3], [10]
Caveats
The labels give no numbers for the size of the added effect.
LimitedHow often is not known

Drugs that change quetiapine or aripiprazole levels

The label states that strong blockers of two liver enzymes raise aripiprazole exposure, including fluoxetine and paroxetine, and that enzyme blockers and inducers change quetiapine exposure.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The aripiprazole label states that strong CYP3A4 inhibitors such as itraconazole and clarithromycin, and strong CYP2D6 inhibitors such as quinidine, fluoxetine and paroxetine, increased aripiprazole exposure, and that carbamazepine decreased it [10]. The quetiapine label states that exposure is increased by CYP3A4 inhibitors such as ketoconazole, itraconazole, indinavir, ritonavir and nefazodone, and decreased by CYP3A4 inducers. It also states that quetiapine may oppose the effects of levodopa and dopamine agonists [3].
Population
Drug interaction studies summarized in labeling [10][3].
Sources
[10], [3]
Caveats
Changes in drug levels, with no rate of harm.

Mixed results1

ModerateStudied in pregnancyCommon

Pregnancy

Not linked to a meaningful rise in birth defects after adjustment in a cohort of 1.3 million pregnancies. The label warns of movement and withdrawal symptoms in newborns.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Congenital malformations were diagnosed in 44.5 per 1,000 births exposed to an atypical antipsychotic in the first trimester and 32.7 per 1,000 unexposed. After adjustment for confounding, the relative risk was 1.05 (95% CI 0.96 to 1.16), with similar findings for cardiac malformations [21]. The quetiapine label states that exposure in the third trimester may cause extrapyramidal or withdrawal symptoms in newborns [3].
Population
1,341,715 pregnancies, 9,258 with an atypical antipsychotic prescription filled in the first trimester [21].
Sources
[21], [3]
Caveats
Observational. The band above is the unadjusted malformation rate in exposed births, which did not differ meaningfully from unexposed births after adjustment. A small increase was seen for risperidone, a drug not covered here.

Claims tested and not found

  1. That aripiprazole prevents new mood episodes in bipolar disorder as reliably as other maintenance drugs. In a network meta-analysis of 33 trials, its estimate against placebo did not reach significance (RR 0.62, 95% credible interval 0.38 to 1.03) [7].
  2. That low-dose quetiapine raises diabetes risk the way full doses are thought to. In 54,616 matched pairs, new type 2 diabetes was no more frequent on low-dose quetiapine than on SSRIs (incidence rate ratio 0.99, 95% CI 0.87 to 1.13) [17].
  3. That atypical antipsychotics in early pregnancy cause birth defects. After adjustment, the relative risk of malformations was 1.05 (95% CI 0.96 to 1.16) across 9,258 exposed pregnancies [21].
  4. That quetiapine adds more sleep than other psychiatric drugs used for sleep. Total sleep time on quetiapine did not differ from other psychiatric drugs (-4.19 minutes, 95% CI -19.43 to 11.05) [13].
  5. That bipolar depression drugs raise response or remission rates over placebo. In a network meta-analysis of 103 trials, no treatment outperformed placebo for response or remission, though several reduced symptom scores [6].

Sources

  1. Leucht S, Leucht C, Huhn M, et al. Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors. American Journal of Psychiatry. 2017. https://doi.org/10.1176/appi.ajp.2017.16121358
  2. Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. The Lancet. 2019. https://doi.org/10.1016/S0140-6736(19)31135-3
  3. U.S. Food and Drug Administration. Seroquel (quetiapine) tablets, prescribing information (AstraZeneca Pharmaceuticals). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0584dda8-bc3c-48fe-1a90-79608f78e8a0
  4. Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. The Lancet. 2012. https://doi.org/10.1016/S0140-6736(12)60239-6
  5. Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. The Lancet. 2011. https://doi.org/10.1016/S0140-6736(11)60873-8
  6. Fornaro M, Di Lorenzo C, Oliva V, et al. Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar depression: A systematic review and dose-related network meta-analysis across different age groups. Journal of Affective Disorders. 2026. https://doi.org/10.1016/j.jad.2026.122160
  7. Miura T, Noma H, Furukawa TA, et al. Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis. The Lancet Psychiatry. 2014. https://doi.org/10.1016/S2215-0366(14)70314-1
  8. Nelson JC, Papakostas GI. Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials. American Journal of Psychiatry. 2009. https://doi.org/10.1176/appi.ajp.2009.09030312
  9. Spielmans GI, Berman MI, Linardatos E, et al. Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. PLOS Medicine. 2013. https://doi.org/10.1371/journal.pmed.1001403
  10. U.S. Food and Drug Administration. Abilify (aripiprazole) tablets, prescribing information (Otsuka America Pharmaceutical). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c040bd1d-45b7-49f2-93ea-aed7220b30ac
  11. Slee A, Nazareth I, Bondaronek P, et al. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. The Lancet. 2019. https://doi.org/10.1016/S0140-6736(18)31793-8
  12. Maher AR, Maglione M, Bagley S, et al. Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-analysis. JAMA. 2011. https://doi.org/10.1001/jama.2011.1360
  13. Lin CY, Chiang CH, Tseng MM, et al. Effects of quetiapine on sleep: A systematic review and meta-analysis of clinical trials. European Neuropsychopharmacology. 2023. https://doi.org/10.1016/j.euroneuro.2022.11.008
  14. Hirsch LE, Pringsheim T. Aripiprazole for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD009043.pub3
  15. Schneider LS, Dagerman KS, Insel P. Risk of Death With Atypical Antipsychotic Drug Treatment for Dementia: Meta-analysis of Randomized Placebo-Controlled Trials. JAMA. 2005. https://doi.org/10.1001/jama.294.15.1934
  16. Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. The Lancet Psychiatry. 2020. https://doi.org/10.1016/S2215-0366(19)30416-X
  17. Højlund M, Lund LC, Andersen K, et al. Association of Low-Dose Quetiapine and Diabetes. JAMA Network Open. 2021. https://doi.org/10.1001/jamanetworkopen.2021.3209
  18. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis. The Journal of Clinical Psychiatry. 2017. https://doi.org/10.4088/JCP.16r10832
  19. Ray WA, Chung CP, Murray KT, et al. Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. New England Journal of Medicine. 2009. https://doi.org/10.1056/NEJMoa0806994
  20. Højlund M, Andersen K, Ernst MT, et al. Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study. World Psychiatry. 2022. https://doi.org/10.1002/wps.21010
  21. Huybrechts KF, Hernández-Díaz S, Patorno E, et al. Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA Psychiatry. 2016. https://doi.org/10.1001/jamapsychiatry.2016.1520

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