What is the initial goal of treatment during an acute phase of a mood episode?

The goal of treatment in bipolar disorder is to stabilise mood. Symptomatic and specific maintenance medications are available for the acute treatment of bipolar disorders. However, maintenance medication remains the cornerstone of management - both for acute episodes and maintenance treatment.

In recent years several new drugs have shown efficacy for the control of manic symptoms and prevention of relapse, but not all are approved for use in bipolar disorders.Trialling medications in the acute phase of the illness - depressed, mixed, hypomanic and manic episodes - helps to find the most effective and tolerable drug or drugs necessary to achieve and maintain euthymic mood in individual patients.

In Australia, several effective drugs for bipolar disorders are subsidised by the Pharmaceutical Benefits Scheme, but some drugs require private prescriptions for use ().

Drugs for the acute management of manic episodes

First-line

- lithium
- valproate
- carbamazepine
- second generation antipsychotics (olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone)

Second-line

- second generation antipsychotic plus lithium or valproate
- lithium plus valproate

Third-line

- electroconvulsive therapy
- clozapine

This list is a composite of recent evidence-based reviews and consensus management guidelines for bipolar mania.,

* indicates no Pharmaceutical Benefits Scheme subsidy for acute mania at time of writing

† the efficacy of clozapine is decreased with smoking

Manic episodes

Drugs recommended for the treatment of manic episodes are listed in .,Lithium, certain anticonvulsantsand several antipsychotics have mood stabilising properties. They treat and prevent mood elevations and, to a lesser extent, help control and prevent depressive episodes.

Episodes of mania typically require inpatient management. Patients with mania require sedation to reduce psychomotor acceleration. So called 'manic exhaustion' had a very high mortality in the premedication era. Prompt restoration of the sleep-wake cycle assists recovery. Often adjunctive benzodiazepines are used for sedation, but it is preferable if the drug chosen to stabilise mood can also serve this function. Managing mania sometimes requires large doses of antimanic drugs in the acute phase, though lower doses may suffice in the maintenance phase. Tolerability is a key factor for subsequent compliance with medications and long-term illness control.

Resolution of the acute episode takes weeks to months. Approximately 50% of patients with mania will respond to monotherapy with any antimanic drug, and around 70-75% will respond to combination therapy. The longer-term evidence on such combination therapy remains limited, and while monotherapy is preferable from compliance, tolerability and cost perspectives, only a third of patients achieve longer-term mood stability on monotherapy.Combination therapy is pragmatically the norm. In rare treatment-resistant cases of mania, where even multiple medications fail to control mania, electroconvulsive therapy and in some cases clozapine may need to be trialled.Acute treatment is generally the start of maintenance therapy.

Hypomanic episodes

Due to the shorter duration of hypomanic episodes, and the lack of marked impairment, hypomania is less frequently the presenting symptom of the illness. Patients with hypomania may feel energetic and creative, and may not need much sleep. They are unlikely to present complaining of feeling 'too well'.

In clinical practice, treatments for manic states are effective in hypomania. Importantly, patients with only hypomanic but no manic episodes (bipolar II pattern) do not tend to progress to bipolar I manic states. Nonetheless, hypomanic episodes are a core precipitant of downward mood destabilisations into major depressive episodes, and thus warrant active treatment, even though depression is invariably the reason patients present for treatment in bipolar II disorder.

Mixed episodes

Mixed states are characterised by elevated and depressed mood mixed together and are among the most difficult mood conditions to identify. Elevated symptoms can be brief, and include racing and 'crowded' thoughts, lability of affect, insomnia and restlessness. Specific pharmacotherapy for mixed states is extrapolated from treatments for mania. One crucial factor is to avoid antidepressants during such mixed states, as they will exacerbate and sometimes trigger the episodes. This can be counterintuitive, when patients present with a dysphoric affect. Mixed states are the most under-recognised of the bipolar specific states, and it is likely that many mixed states are triggered by antidepressants. If a patient's agitated depressive symptoms seem to worsen with antidepressants, consider the possibility of a mixed state and bipolar diagnosis.

Depressive episodes

Drugs for the treatment of bipolar depressive episodes are listed in ., The best current evidence for efficacy in bipolar depression exists for lithium, quetiapine and lamotrigine.

Antidepressants place patients at risk of switching to elevated phases of the disorder and rapid cycling patterns. Although the results of a recent study do not support the use of adjunctive antidepressant therapy in the acute treatment of bipolar depression, this topic remains very controversial. Many patients with bipolar depression will not respond to changes in mood stabilising medicines alone. They may need an antidepressant, but this must be taken with a mood stabilising drug. Frequent regular mental state review is necessary for any patient taking this combination to detect destabilisation, and non-response or loss of response to the antidepressant. Patients should not simply be left on the antidepressant long term without review.

Considerable controversy exists as to how long antidepressants should be continued, and there is no good evidence of efficacy in the maintenance phase. What is clear is the need for monitoring of the patient's mental state and dose reduction or cessation of the antidepressant if elevated symptoms emerge.

Should an antidepressant be needed, low-dose selective serotonin reuptake inhibitors are usually adequate and may have less propensity to induce elevated phases of the disorder.As fluoxetine has a five-week washout period it is best avoided in bipolar conditions in case a manic, mixed or hypomanic mood switch necessitates cessation.

Table 2

Drugs for acute management of bipolar depressive episode

First-line

- lithium, quetiapine or lamotrigine monotherapy
- lithium or valproate with selective serotonin reuptake inhibitor or bupropion*
- olanzapine with selective serotonin reuptake inhibitor
- lithium with valproate

Second-line

- add-on or switch to a second mood stabiliser and/or add a selective serotonin reuptake inhibitor (if patient is not already taking one)

Third-line

- mood stabiliser with serotonin noradrenaline reuptake inhibitor or tricyclic antidepressant or monoamine oxidase inhibitor
- electroconvulsive therapy

This list is a composite of recent evidence-based reviews and local consensus management guidelines for bipolar depression.,

* an antidepressant re-patented in Australia for smoking cessation

†lithium, valproate, carbamazepine, lamotrigine, olanzapine or quetiapine. Keep patient on whichever mood stabilising drugs have worked during elevated phases of illness.

Which ones are considered first

What is the best treatment for the acute manic phase?

What is the primary goal of the acute phase of treatment for bipolar disorder?

Which of the following is the first