Long-term treatment aims to prevent either manic or depressive episodes. Structured psychological interventions (individual, group or family) are designed to prevent relapse by improving knowledge of bipolar disorder. Group psychoeducation appears to be a highly effective adjunct to pharmacotherapy in relapse prevention.

Medication that has been effective during episodes of mania or bipolar depression is often continued as long-term therapy. Lithium, the most effective long-term treatment for bipolar disorder, is associated with a reduced risk of suicide, and is the treatment of choice for most patients. Lithium is not recommended for patients with poor adherence as rapid discontinuation may increase the risk of relapse. When lithium is ineffective, poorly tolerated or used in a patient unlikely to be adherent, valproate or an antipsychotic may be prescribed. 

Patients primarily affected by mania should be treated with the predominantly antimanic medicines lithium, olanzapine, quetiapine, risperidone long-acting injection or valproate. Those primarily affected by depressive episodes should be prescribed lamotrigine, lithium or quetiapine. 

In bipolar I disorder, lamotrigine is usually used in combination with an antipsychotic medicine. In patients with bipolar II disorder, lamotrigine and quetiapine may be effective monotherapies. 

Antipsychotics 

The main mode of action of antipsychotics is antagonism at dopamine D2 receptors but there are other pharmacological differences between them, hence their use in different phases of bipolar disorder. 

Lithium

Lithium modifies the production and turnover of neurotransmitters, particularly serotonin, and may also block dopamine receptors. 

Lithium has side-effects affecting the kidneys and the thyroid gland, so renal and thyroid function needs to be assessed prior to starting with it, and repeated every six months during treatment. Patients with cardiovascular disease or risk factors should have an electrocardiogram (ECG) prior to starting lithium treatment.

Patients on lithium should have a record booklet which prescribers and pharmacists can use to check that blood tests are monitored regularly. 

Valproate

There are significant risks for the unborn child if valproate is taken during pregnancy, including the risk of congenital malformations and developmental delay. Use should therefore be avoided in women of child-bearing age. Valproate is also associated with polycystic ovary disease so should not be considered in females under 18 years of age. Semi sodium valproate (Depakote) is the only valproate preparation licensed for the treatment of manic episodes associated with bipolar disorder.

Lamotrigine 

Lamotrigine can cause a rash, which can lead to serious conditions such as Stevens-Johnson syndrome. This side-effect is most common in the first eight weeks of therapy so the dose should be increased very slowly when treatment is started to minimise risk. When used with valproate, the titration should be even slower at half the rate.