The primary treatments for bipolar disorder are pharmacological, and often involve second generation antipsychotic drugs such as aripiprazole. Aripiprazole is is a partial agonist of dopamine D2 and serotonin 5-HT1A receptors and an antagonist of 5-HT2A receptors. It has a distinct receptor-binding profile compared to other second generation antipsychotic drugs.

What is the evidence for aripiprazole as a treatment for bipolar disorder?

Mania and psychotic symptoms

Moderate quality evidence suggests a small effect of greater improvement with aripiprazole than with placebo. The effect for mania is large in pediatric patients. There were no differences in mania symptoms between aripiprazole and other medications, however, there were large effects of more switching to mania with aripiprazole than with quetiapine or ziprasidone.

Depressive symptoms

Moderate to high quality evidence suggests no significant differences between aripiprazole and placebo for depression. Moderate quality evidence suggests less improvement in depression, less response to treatment, and less likelihood of remission with aripiprazole than with lurasidone.

Overall symptoms and prevention of relapse

Moderate quality evidence suggests greater overall improvement in symptoms with aripiprazole than with haloperidol or lithium. There were medium-sized effects of fewer relapses with aripiprazole + valproate or aripiprazole + lamotrigine than with placebo. There were also fewer relapses with aripiprazole + valproate than with paliperidone or imipramine. Also see the topics on relapse prevention and polypharmacy.

Side effects

Moderate quality evidence suggests more high-density lipoprotein, sedation, extrapyramidal symptoms, constipation, nausea, vomiting, anxiety, salivation, fatigue, insomnia, and pain in the extremities with aripiprazole than with placebo. However, there was less hyperprolactinemia, less elevated fasting glucose, less increased appetite, and less total cholesterol with aripiprazole.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve second generation antipsychotic drugs, such as asenapine. Based on its high affinity for seratonin receptors, asenapine has been proposed as a treatment for bipolar disorder.

What is the evidence for asenapine as a treatment for bipolar disorder?

Moderate to high quality evidence suggests small to medium-sized effects of greater improvement in mania and depression symptoms with asenapine monotherapy than with placebo. However, there were more extrapyramidal side effects, somnolence, dizziness, sedation, blood glucose, and weight gain with asenapine.

Moderate to high quality evidence suggests no differences between asenapine monotherapy and olanzapine monotherapy for mania symptoms. There was no analysis of depression symptoms. There was more dizziness and parkinsonism with asenapine, and more weight gain and higher prolactin levels with olanzapine.

Also see the topic on relapse prevention.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve second generation antipsychotic drugs, such as cariprazine. Based on its high affinity for dopamine receptors, cariprazine has been proposed as a treatment for bipolar disorder.

What is the evidence for cariprazine as treatment for bipolar disorder?

High quality evidence suggests cariprazine is associated with greater improvements in mania and depression than placebo, but is associated with more adverse effects including akathisia, tremor, restlessness, and weight gain.

Moderate quality evidence finds similar improvement in depression symptoms with low (0.75-1.5 mg) and high (3 mg) dose cariprazine.

Moderate quality evidence finds a medium-sized effect of greater improvement in mania symptoms with cariprazine than with topiramate, but less improvement when compared to tamoxefin.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve second generation antipsychotics. Based on its high affinity for both serotonin and dopamine receptors, clozapine has been proposed as a treatment for the disorder.

What is the evidence for clozapine?

Moderate to low quality evidence suggests improved symptoms and reduced hospitalisation, suicidal ideation, and aggressive behaviour, and also improved social functioning with clozapine in people with treatment-resistant bipolar disorder. There were no differences in efficacy for mania symptoms between clozapine and olanzapine or quetiapine.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve antipsychotic drugs such as the first-generation antipsychotic haloperidol.

What is the evidence for haloperidol for bipolar disorder?

Moderate quality evidence suggests medium-sized effects of greater improvement in acute mania symptoms with haloperidol than with placebo, topiramate, or lamotrigine, although there was more improvement with tamoxefin than with haloperidol. There was more all-cause discontinuation with haloperidol than with olanzapine, and less all-cause discontinuation with haloperidol than with topiramate.

Moderate to low quality evidence suggests no significant differences in rates of switching to depression between haloperidol and aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. There were also no consistent differences in rates of somnolence between haloperidol and placebo, olanzapine, quetiapine, risperidone, or ziprasidone.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve antipsychotic drugs such as second-generation antipsychotic, lurasidone.

What is the evidence for lurasidone as treatment for bipolar disorder?

Moderate to high quality evidence suggests significant, small to medium-sized effects of greater improvement in depression symptoms and better response to treatment with lurasidone adjunctive to mood stabilisers than with placebo adjunctive to mood stabilisers. Moderate to low quality evidence also suggests higher rates of remission with adjunctive lurasidone. There were no differences between adjunctive lurasidone and placebo in the number of adverse events, rates of switching to mania, or withdrawal from treatment for any reason.

Moderate quality evidence suggests greater improvement in depression symptoms, response to treatment, and remission with lurasidone monotherapy than with placebo, aripiprazole or ziprasidone monotherapy, with no differences between lurasidone and olanzapine or quetiapine monotherapy. There was less weight gain and somnolence with lurasidone than with ziprasidone or quetiapine; less weight gain with lurasidone than with olanzapine, but more switching to mania with lurasidone than with quetiapine.

Moderate to high quality evidence suggests no differences in depression symptoms between low (20-60 mg) and high (80-120 mg) dose lurasidone monotherapy.

Also see the topics on relapse prevention and polypharmacy.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve antipsychotic drugs such as the second-generation antipsychotic, olanzapine.

What is the evidence for olanzapine as treatment for bipolar disorder?

Symptoms

Moderate to high quality evidence suggests significant, small to medium-sized effects of greater improvement in depression symptoms and better response to treatment with olanzapine than with placebo. Olanzapine + fluoxetine resulted in greater improvement in depression symptoms and response than olanzapine alone.

Moderate to high quality evidence suggests small to medium-sized effects of greater improvement in acute mania symptoms with olanzapine than with placebo, particularly for people with more severe symptoms at the start of treatment. Moderate quality evidence suggests greater improvement in acute mania symptoms with olanzapine than with lithium topiramate or lamotrigine, although there was greater improvement in mania symptoms with tamoxefin than with olanzapine.

Moderate to low quality evidence suggests intramuscular olanzapine was more effective at reducing agitation than placebo or lorazepam.

Relapse

Moderate to high quality evidence suggests a medium-sized effect of fewer relapses with olanzapine than with placebo. There were small effects of fewer relapses (any) with olanzapine compared to lamotrigine, paliperidone and imipramine.

Side effects

Moderate quality evidence suggests more weight gain with olanzapine than with lurasidone. Olanzapine was more likely to elevate prolactin levels than placebo. Moderate to low quality evidence suggests olanzapine may be more likely to elevate prolactin levels than risperidone, and less likely to elevate prolactin levels than valproate. There was less all-cause discontinuation with olanzapine than with placebo, cariprazine, lithium, carbamazepine, asenapine, verapamil, lamotrigine, licarbazepine and topiramate. There were no differences between olanzapine and placebo in rates of switching to mania.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve antipsychotic drugs such as the second-generation antipsychotic, paliperidone.

What is the evidence for paliperidone as treatment for bipolar disorder?

Moderate quality evidence suggests small to medium-sized effects of greater improvement in acute mania symptoms with paliperidone than with placebo or topiramate, although there was greater improvement with tamoxefin than with paliperidone. There was less all-cause discontinuation with paliperidone than with topiramate.

Moderate to low quality evidence suggests suggests there may be lower rates of somnolence with paliperidone than with quetiapine. There were also no consistent differences in rates of weight gain between paliperidone and placebo. Paliperidone may be more likely to elevate prolactin levels than placebo, quetiapine or olanzapine.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve second-generation antipsychotic drugs, such as quetiapine. Based on its high affinity for dopamine and serotonin receptors, quetiapine has been proposed as a treatment for bipolar disorder.

What is the evidence for quetiapine as treatment for bipolar disorder?

Symptoms and functioning

Moderate to high quality evidence suggests quetiapine was more effective than placebo for symptoms, response, remission, quality of life, sleep, and disability in adults, but not in children, with bipolar disorder (also see the treatments for children topic). There was small effects of greater improvement in depression symptoms and greater response to treatment with quetiapine than with paroxetine or risperidone. Moderate quality evidence suggests quetiapine may also be more effective than lithium for depression symptoms.

Moderate quality evidence suggests small to medium-sized effects of greater improvement in acute mania symptoms with quetiapine than with placebo or topiramate, although there was greater improvement in mania symptoms with tamoxefin than with quetiapine. High quality evidence suggests no differences in depression symptoms, response or remission between low (300 mg) and high (600 mg) dose quetiapine.

Relapses

Moderate quality evidence suggests a medium-sized effect of fewer relapses with quetiapine than with placebo, lamotrigine or imipramine. Also see the topics on relapse prevention and polypharmacy.

Side effects

Compared to placebo, moderate quality evidence suggests quetiapine is associated with higher rates of extrapyramidal side effects, somnolence, sedation, dizziness, fatigue, constipation, dry mouth, increased appetite, weight gain, and all-cause discontinuation of treatment. But there may be lower cholesterol and LDL levels, and lower rates of treatment-emergent mania and headache with quetiapine.

Compared to other medications, there may be more somnolence with quetiapine than with paliperidone or lurasidone; more weight gain with quetiapine than with lithium or lurasidone; less switching to mania with quetiapine than with paroxetine, lamotrigine, lurasidone or aripiprazole; more switching to mania with quetiapine than with risperidone; and less adverse events in general with quetiapine than with paroxetine. There may also be less all-cause discontinuation of treatment with topiramate than with quetiapine.

November 2021

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The treatment of bipolar disorder is complex due to the presence of varying configurations of symptoms in patients. The primary treatments for bipolar disorder are pharmacological, and often involve second generation antipsychotic drugs, such as risperidone. Based on its affinity for dopamine and serotonin receptors, risperidone has been proposed as a treatment for bipolar disorder.

What is the evidence for risperidone as treatment for bipolar disorder?

Symptoms

Moderate quality evidence suggests small to medium-sized effects of greater improvement in acute mania symptoms with risperidone than with placebo, aripiprazole, lithium, valporate, lamotrigine, licarbazepine, or topiramate, although there was greater improvement with tamoxefin than with risperidone. Moderate to high quality evidence suggests small to medium-sized effects of greater improvement in depression symptoms and better response to treatment with quetiapine than with risperidone.

Relapses

Moderate quality evidence suggests a small effect of fewer relapses (any) with risperidone than with placebo.

Side effects

Moderate quality evidence suggests more somnolence and all cause treatment discontinuation with risperidone than with placebo. There was also less all-cause discontinuation with topiramate than with risperidone and more switching to mania with quetiapine than with risperidone.

Moderate to low quality evidence suggests greater increases in prolactin levels with risperidone than with lithium or valproate.

November 2021

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