Treatment of bipolar disorder

For further details see Mental Health Prescribing Forum Prescribing Guideline PG13 Pharmacological Treatment of Bipolar Disorder

These guidelines cover three distinct therapeutic areas:

  • Acute manic/ hypomanic episodes
  • Bipolar depression
  • Long term maintenance therapy for bipolar disorder

These guidelines only cover pharmacological management and other resources should be examined for appropriate psychological interventions in bipolar disorder, where they exist.

General considerations

Healthcare professionals should fully involve individuals in decisions about their treatment and care, and determine treatment plans in collaboration with the individual, carefully considering the experience and outcome of previous treatment(s) together with individual preference.

Contraception and the risks of pregnancy (including the risks of relapse, damage to the foetus, and the risks associated with stopping or changing medication) should be discussed with all women of child-bearing potential, regardless of whether they are planning a pregnancy. They should be encouraged to discuss pregnancy plans with their doctor.

People experiencing a manic episode, or severe depressive symptoms, should normally be seen again within a week of their first assessment, and then regularly at appropriate intervals, for example, every 2–4 weeks in the first 3 months and less often after that, if response is good.

A key component to successful long term management of bipolar disorder is to engage the individual in recognising triggers or relapse signs e.g. insomnia. A Wellness Recovery Action Plan (WRAP) is an excellent tool for facilitating this work

Acute hypomania / mania

If the individual is taking an antidepressant stop this as soon as safe to do so. Bear in mind withdrawal syndromes but this is often overridden by clinical need to halt the antidepressant quickly.

Antipsychotics

Antipsychotics are commonly used in acute episodes of mania but are also now licensed as mood stabilisers in their own right. This consideration is important when choosing an initial antipsychotic. Certain typical antipsychotics (e.g. haloperidol) are also licensed for acute mania but are not specifically included here due to their side effect profile.

See section 4.2 Drugs used in psychoses and related disorders.

Risperidone
  • Not licensed for long-term maintenance
Olanzapine
  • Licensed for long-term use but consider long-term side effects
Quetiapine
  • Consider when other treatments ineffective or not tolerated

Not taking antimanic medication

When making the choice, prescribers should take into account preferences for future prophylactic use and the relevant side-effect profile.

See section 4.2 Drugs used in psychoses and related disorders

Antipsychotic (see above)

  • If severe manic symptoms or marked behavioural disturbance as part of the syndrome of mania
  • If ineffective, augmenting it with valproate or lithium should be considered

Valproate

  • If symptoms have responded to these drugs before, and the person has shown good compliance
  • Do not prescribe routinely in women of child-bearing age but if no alternative ensure adequate advice on need for contraception provided and the risks of valproate during pregnancy should be explained

Lithium

  • If symptoms have responded to these drugs before, and the person has shown good compliance
  • Only if symptoms are not severe because it has a slower onset of action than antipsychotics and valproate

Lorazepam

  • In the initial management of acute behavioural disturbance or agitation, the short-term use of lorazepam should be considered in addition to the antimanic agent. Other benzodiazepines are equally effective
  • See section 4.8 Antiepileptic drugs

Taking antimanic medication

For individuals who present with severe mania when already taking lithium or valproate, adding an antipsychotic should be considered at the same time as gradually increasing the dose of lithium or valproate. Already taking:

Antipsychotic

Valproate

Lithium

  • Check plasma lithium levels
  • If levels are suboptimal for treating acute mania (below 0.8 mmol per litre), increase dose to a maximum blood level of 1.0 mmol per litre.
  • If the response is not adequate, augmenting lithium with an antipsychotic or valproate should be considered
  • See section 4.2 Drugs used in psychoses and related disorders

Carbamazepine

  • Do not increase the dose routinely
  • Augment with antipsychotic, be mindful of interactions (see BNF)
  • See section 4.8 Antiepileptic drugs

Acute/mixed episodes

Treat as a hypomanic/manic episode and avoid prescribing antidepressants. Closer monitoring of suicidality is recommended, e.g. weekly follow up.

Bipolar depression

All episodes of depression where there is no history suggesting bipolar affective disorder should be treated in accordance with the Unipolar Depression guidance.

Antidepressants carry the risk of 'switching' to manic states when used in bipolar disorder, and they may be involved in cycle acceleration (mood destabilisation). When prescribing an antidepressant, an anti-manic agent should also be prescribed and specialist advice sought.

Patient NOT taking antimanic medication

Quetiapine

SSRIs

  • Associated with fewer switches in mood than other antidepressants so should be used preferentially. Stop the antidepressant once symptoms resolved. If possible avoid where there is history of switching to manic states or prescribe with an antimanic or mood stabilising drug
  • See section 4.3 Antidepressant drugs

Lithium

Lamotrigine

  • First line in less severe depressive episodes (i.e. not bipolar I disorder) where rapid response not required owing to long titration time.
  • See section 4.8 Antiepileptic drugs

Patient taking antimanic medication

Ensure adequate doses of medicines and that serum levels of lithium are within the therapeutic range.

Ensure current choice of long-term treatments is likely to protect the patient from manic relapse (e.g. lithium, carbamazepine, valproate, antipsychotic).

Rapid-cycling bipolar disorder

A full therapeutic history is necessary to identify a treatment which is less associated with mood switching previously, or to identify an inadequate trial of treatment. Treatment trials should last 6 months, focus on optimising long-term treatments and not in response to individual episodes or symptoms.

Long term maintenance

  • Long term treatment should be dictated by the individual's history and the course of their illness
  • Lithium has been shown to reduce the incidence of suicide in bipolar affective disorder. See below for guidance on prescribing lithium
  • Long-term drug treatment should normally continue for at least 2 years after an episode of bipolar disorder. NICE recommends extending the treatment period if the person has risk factors for relapse, such as a history of frequent relapses or severe psychotic episodes, co-morbid substance misuse, on-going stressful life events, or poor social support. The choice of treatment and treatment duration should be discussed with the patient and there should be regular reviews
  • Long-acting depots are not recommended in bipolar disorder except where individuals who responded well to antipsychotics have suffered a relapse due to non-compliance with oral treatment

Mania predominant (monotherapy or combinations): Lithium, Valproate, Olanzapine

Depression predominant: Quetiapine, Lamotrigine, Lithium, SSRIs with suitable antimanic prophylactic agent

Lithium

Lithium has a narrow therapeutic range and monitoring is essential. Specialist services should provide the prescriber with target lithium concentrations and monitoring schedule.

Lithium monitoring is part of the Quality and Outcomes Framework (QOF).

Clinically appropriate monitoring which is accordance with the product licence should be undertaken and should include:

  • Thyroid function
  • Renal function
  • ECG
  • Weight
  • Calcium
  • Lithium levels- see BNF and SPC for latest guidance.

Drug interactions- see BNF

A DPT protocol on lithium is available: CP05 Prescribing and Monitoring of Lithium Therapy

The results of the biochemical tests should be to hand when prescribing lithium in accordance with the NPSA Patient Safety Alert Safer Lithium Therapy.

All individuals prescribed lithium must have a lithium treatment information pack (Purple book). This must be completed by the prescriber, including information about dose and relevant blood testing.

Prescribing in Pregnancy

Prescribers are advised to seek specialist advice when a pregnancy is being planned. The National Teratology Information Service is available for NHS health professionals on 0844 892 0909 (8.30 – 17.00 Monday to Friday).

If an unplanned pregnancy occurs:

  • the pregnancy should be confirmed as quickly as possible
  • the woman should be advised to stop taking valproate, carbamazepine and lamotrigine
  • if the pregnancy is confirmed in the first trimester, and the woman is stable, lithium should be stopped gradually over 4 weeks, and the woman informed that this may not remove the risk of cardiac defects in the foetus
  • if the woman remains on lithium during pregnancy serum lithium levels should be checked every 4 weeks, then weekly from the 36th week, and less than 24 hours after childbirth; the dose should be adjusted to keep serum levels within the therapeutic range, and the woman should maintain adequate fluid intake
  • an antipsychotic should be offered as prophylactic medication
  • offer appropriate screening and counselling about the continuation of the pregnancy, the need for additional monitoring and the risks to the foetus if the woman stays on medication

If a woman with bipolar disorder continues with an unplanned pregnancy, the newborn baby should have a full paediatric assessment, and social and medical help should be provided for the mother and child.

MHRA Drug Safety Update (February 2016): Valproate and risk of abnormal pregnancy outcomes: new communication materials. MHRA Drug Safety Update (April 2017): Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures.

  1. ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental disorders and 10% risk of birth defects and are using effective contraception
  2. valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated; migraine is not a licensed indication
  3. valproate use in women and girls of childbearing potential must be initiated and supervised by a specialist experienced in managing epilepsy or bipolar disorder
  4. carefully balance the benefits of valproate treatment against the risks when prescribing valproate for the first time, at routine treatment reviews, when a female child reaches puberty and when a woman plans a pregnancy or becomes pregnant
  5. you must ensure that all female patients are informed of and understand:
    1. risks associated with valproate during pregnancy
    2. need to use effective contraception
    3. need for regular review of treatment
    4. the need to rapidly consult if she is planning a pregnancy or becomes pregnant

Patient Safety Alert to further highlight risks to the unborn child and support the safety of girls and women taking valproate

The Medicines and Healthcare Products Regulatory Agency's (MHRA) Toolkit on the risks of valproate medicines in female patients, provides resources to ensure female patients are better informed about the risks of taking valproate medicines during pregnancy.

Patient focussed resources

 

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