Medication use during pregnancy requires careful consideration of the mother’s risk of illness relapse against the risk of harm or complications for the developing infant if medication is to be continued.

What is the evidence for medication use during pregnancy and breastfeeding in women with bipolar disorder?

Moderate quality evidence finds lithium use during pregnancy was associated with small increased risks of any congenital anomaly, cardiac congenital anomalies, and a medium-sized risk of more spontaneous abortion compared to no lithium use. Note that the findings for cardiac congenital anomalies and spontaneous abortion were not significant when lithium use was compared to no lithium use only in bipolar patients (not general population samples). The finding for any congenital anomaly remained in that comparison. There were no increased risk of preterm birth or low birth weight.

Moderate to low quality evidence finds a small increased risk of heart defect or lower birth weight in infants exposed to antipsychotics in utero, and a small increased risk of preterm delivery. There is also a small increased risk of neuromotor deficits in early childhood with exposure to antipsychotics in utero. However, studies did not allow correction for other medications, genetic predisposition, or other confounding effects.

There were no differences in the odds of autism spectrum disorders in the offspring of mothers with SSRI antidepressant exposure during pregnancy compared with mothers with no antidepressant exposure during pregnancy.

Low quality evidence is unsure of the risk of relapse following discontinuation of mood stabilisers during pregnancy. Review authors conclude that for severe conditions of bipolar disorder, close monitoring, support, and prophylactic medication during pregnancy and the postpartum period is recommended. For women with stable bipolar disorder, well-planned and slow discontinuation of mood stabilisers before pregnancy could be commenced. For unplanned pregnancies, slow discontinuation is particularly important. Medication should be re-started soon after delivery, as the risk of postpartum relapse is high.

October 2021

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Agitation and/or aggression are sometimes observed during a psychiatric emergency such as in onset of acute psychosis. Agitation typically includes irritability and restlessness, motor or verbal hyperactivity, uncooperativeness, and occasionally aggressive gestures or behaviour. This can pose a risk both to the individual, as well as the attending health care professionals, and so is important to manage this behaviour and prevent potential harm.

What is the evidence for treatments for aggression and agitation?

Moderate to low quality evidence suggests intramuscular olanzapine (10mg x 2 doses + 5mg x 1 dose), inhaled loxapine (5 or 10mg), or intramuscular aripiprazole (9.75 or 15mg) are more effective at reducing agitation in people with bipolar disorder than placebo or lorazepam.

November 2021

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Bipolar II disorder is a common, recurrent, and disabling psychiatric illness. The lifetime incidence ranges from 1% to 11% depending on the method of diagnosis. DSM-IV defines bipolar II disorder as a lifetime history of at least one episode of major depression plus at least one episode of hypomania. By definition, individuals with bipolar II disorder never experience full-blown mania, unlike those with a diagnosis of bipolar I disorder. Bipolar II disorder is characterised by multiple and often protracted depressive episodes and a lower probability of returning to premorbid levels of functioning between episodes.

What is the evidence for treatments for bipolar II disorder?

Moderate to low quality evidence suggests the antipsychotic quetiapine may be an effective treatment for bipolar II depression. Low quality evidence is uncertain as to the benefits of other medications.

November 2021

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Bipolar disorders are a group of disorders characterised by episodes of depression and mania or hypomania. Bipolar disorders described in the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, version 5) include bipolar I disorder involving severe depression and mania, bipolar II disorder involving depression and hypomania (less severe mania), and cyclothymic disorder involving many mood swings, with hypomania and depressive symptoms occurring often and fairly constantly.

Major depressive disorder characterised in the DSM-5 involves five (or more) of the following symptoms to be present and represent a change from previous functioning. At least one of the symptoms must be either depressed mood or loss of interest or pleasure, with no history of mania.
• Depressed mood most of the day, nearly every day
• Diminished interest/pleasure in all, or almost all, activities most of the day, nearly every day
• A change of more than 5% of body weight in a month or decrease/increase in appetite
• Insomnia or hypersomnia
• Fatigue or loss of energy
• Psychomotor agitation or retardation that is observable by others
• Feelings of worthlessness or excessive or inappropriate guilt
• Diminished ability to think or concentrate, or indecisiveness
• Recurrent thoughts of death or a suicide attempt or plan

What is the evidence for differences in treatment response between bipolar and unipolar depression?

Moderate to low quality evidence suggests no differences in depression severity between people with bipolar or unipolar depression after treatment with antidepressants. There are small, but clinically significant effects of improved depression symptoms with any antidepressant for major depressive disorder. For bipolar disorder, the antidepressant paroxetine, antipsychotics aripiprazole, lurasidone, olanzapine, quetiapine, and ziprazidone, and mood stabilisers lithium, lamotrigine, and divalproex also have small, but clinically significant effects for improving depression.

November 2021

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Bipolar disorder is a chronic psychiatric illness that can have devastating effects on individuals and their families. It is the sixth leading cause of disability worldwide, with prevalence estimated to be around 1% in the general adult population. The age of onset of bipolar disorder typically occurs during early adulthood, although onset can occur in childhood or adolescence. Bipolar disorder in childhood and adolescence is commonly associated with impairment in multiple domains, including increased risk of psychiatric hospitalisation, antisocial behaviour, addictions, and suicidal behaviour. There is a need to optimise treatments for childhood patients for whom medication use could be long-term, with concerns about potential overuse and side effects in a population who are undergoing relevant biological, psychological, and social maturational changes.

What is the evidence on pharmaceutical treatments for childhood bipolar disorder?

Moderate quality evidence suggests combined treatment with an anticonvulsant or lithium plus a second-generation antipsychotic was significantly more effective for clinical response than individual treatments.

Moderate to high quality evidence suggests a medium-sized effect of improved mania symptoms with second-generation antipsychotics aripiprazole, olanzapine, risperidone, and ziprasidone compared to placebo. Moderate quality evidence suggests no differences in depression symptoms between the antipsychotic quetiapine and placebo.

Moderate to low quality evidence finds a small effect of improved mania symptoms with mood stabilisers divalproex, lithium, oxcarbazepine, and topiramate compared to placebo.

Second generation antipsychotics may cause more weight gain and drowsiness than mood stabilisers, while mood stabilisers may cause more akathisia (inner restlessness).

Antipsychotics may cause more weight gain and drowsiness than mood stabilisers, while mood stabilisers may cause more akathisia (inner restlessness).

November 2021

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Cognitive symptoms in people with bipolar disorder may be apparent in many cognitive domains, including executive function, memory, and attention, and may develop prior to the core mood symptoms of bipolar. Cognitive symptoms are highly disabling and may predict poor functional outcomes

What is the evidence for pharmaceutical treatments for cognitive symptoms?

Low quality evidence is unclear of the benefits of pharmaceutical treatments for cognition in people with bipolar disorder. Review authors conclude that the findings are disappointing due to study methodological issues.

November 2021

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Several treatments have been targeted to people with ‘dual diagnosis’, which is having both a psychiatric disorder and a substance use disorder. Studies investigate the availability and effectiveness of treatments for either diagnosis, including symptom severity, substance use, social functioning, quality of life, and also, cognition.

What is the evidence for treatments for dual diagnosis?

Moderate to high quality evidence quetiapine significantly improved manic symptoms, but not depression symptoms compared to placebo. There were no effects for mania or depression of mood stabilisers, citicoline, or acamprosate compared to placebo. Lower quality evidence from small trials suggests the anticonvulsants valproate and lamotrigine may also improve mood and reduce substance use.

November 2021

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The prevalence of mania among 65-year-olds ranges from 0.1% to 0.4%. Older people with bipolar disorder constitute between 5 and 20% of patients presenting for acute treatment at geriatric psychiatry services. Although the psychopathologic manifestations of mania are similar in older and younger patients, response to treatment can be extremely variable and the disorder has a greater impact and higher mortality rate in elderly patients than in younger patients.

What is the evidence for treatments for older people with bipolar disorder?

Moderate to low quality evidence suggests lithium may be effective and well-tolerated in older patients with bipolar disorder.

November 2021

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Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively, we will endeavour to conduct our own review to fill this gap in the Library.

November 2021

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People deemed at high risk for bipolar disorder can be identified by having a family history of a mood disorder and/or having subclinical symptoms that are not severe enough for a diagnosis. Subclinical symptoms include depression, difficulty with concentration, episodic mood swings, anxiety, sleep disturbances, and sensitivity to stress. Familial risk accompanied by mood dysregulation or other mood symptomatology could help define the population at high risk of bipolar disorder. Early intervention involves identifying and treating these high-risk individuals as repeated mood episodes put people at risk of poor symptomatic and functional recovery.

What is the evidence for medication in people at high risk for bipolar disorder?

Moderate to low quality evidence finds aripiprazole was significantly superior to placebo in improving mood, ADHD, and functioning scores in children and adolescents with a parent with bipolar disorder. There were no effects of valproate compared to placebo.

November 2021

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