Treatment of bipolar disorder

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

Quetiapine may be used for the treatment of depressive episodes in bipolar disorder. There is some evidence for the use of lamotrigine, but this use is unlicensed.

If the patient has frequent relapses, or symptoms continue to cause functional impairment, switching to an alternative monotherapy or adding a second prophylactic agent (lithium, valproic acid, olanzapine,) should be considered. Clinical state, side effects and, where relevant, blood levels should be monitored closely. Possible combinations are lithium with valproic acid, lithium with olanzapine, and valproic acid. Please refer to: NICE CG38 Bipolar disorder (July 2006)

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

See 4.2 Drugs used in psychoses and related disorders

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.

Risperidone

  • 1st line, not licensed for long-term maintenance

Olanzapine

  • 2nd line, licensed for long-term use but consider long-term side effects

Quetiapine / aripiprazole

  • 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.

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 (See 4.2 Drugs used in psychoses and related disorders)

  • If symptoms have responded to these drugs before, and the person has shown good compliance
  • Use of valproate in pregnancy is contraindicated for bipolar disorder
  • In April 2018 the MHRA issued a strengthened Drug Safety Update for valproate medicines which are now contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met and only if other treatments are ineffective or not tolerated, as judged by an experienced specialist. All women and girls (and their parent, caregiver, or responsible person, if necessary) must be fully informed of the risks and the need to avoid exposure to valproate medicines in pregnancy.
    • GPs must identify and recall all women and girls who may be of childbearing potential, provide the Patient Guide and check they have been reviewed by a specialist in the last year and are on highly effective contraception.
    • Specialists must book in review appointments at least annually with women and girls under the Pregnancy Prevention Programme and re-evaluate treatment as necessary; explain clearly the conditions as outlined in the supporting materials; and complete and sign the Risk Acknowledgement Form — copies of the form must be given to the patient or patient/caregiver/responsible person and sent to their GP.
    • See MHRA Drug Safety Update (April 2018) for further details.

Lithium (See 4.2 Drugs used in psychoses and related disorders)

  • 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

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 (see above)

  • Check dose and increase if necessary
  • If no signs of improvement, the addition of lithium or valproate should be considered

Valproate

  • Increase the dose until: symptoms start to improve or side effects limit further dose increase.
  • If there are no signs of improvement, consider augmenting with an antipsychotic

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

Carbamazepine (see 4.8 Antiepileptic drugs)

  • Do not increase the dose routinely
  • Augment with antipsychotic, be mindful of interactions (see BNF)
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.

Not taking antimanic medication

Quetiapine See 4.2 Drugs used in psychoses and related disorders

  • Consider in severe depressive episodes of proven bipolar disorder (NB: give once daily; not XL preparation unless immediate release not tolerated)

SSRIs (see 4.3 Antidepressant drugs)

  • 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

Lithium See 4.2 Drugs used in psychoses and related disorders

  • May also be considered in less severe cases or in association with an antidepressant to try to prevent switching

Lamotrigine (see 4.8 Antiepileptic drugs)

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

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.

  1. For Western locality please refer to Shared Care Information
  2. For South Devon and Torbay CCG please refer to Shared Care Information

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.

Valproate Medicines

The use of valproate in pregnancy is contraindicated for bipolar disorder.

In April 2018 the MHRA issued a strengthened Drug Safety Update for valproate medicines which are now contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met and only if other treatments are ineffective or not tolerated, as judged by an experienced specialist. All women and girls (and their parent, caregiver, or responsible person, if necessary) must be fully informed of the risks and the need to avoid exposure to valproate medicines in pregnancy.

  • GPs must identify and recall all women and girls who may be of childbearing potential, provide the Patient Guide and check they have been reviewed by a specialist in the last year and are on highly effective contraception.
  • Specialists must book in review appointments at least annually with women and girls under the Pregnancy Prevention Programme and re-evaluate treatment as necessary; explain clearly the conditions as outlined in the supporting materials; and complete and sign the Risk Acknowledgement Form — copies of the form must be given to the patient or patient/caregiver/responsible person and sent to their GP.
  • See MHRA Drug Safety Update (April 2018) for further details.

Children and adolescents

Very few psychotropic drugs are licensed for use in children. This should be carefully explained and informed consent sought from patients and their parents/carers.

Children are generally more ill than their adult counterparts and will often require longer periods of treatment before responding. For full guidance on drugs, indications, contraindications, dose, side-effects and required period of treatment, please refer to the latest BNF for children

Acute mania

Follow the recommendations for treating acute mania in adults except that drugs should be started at lower doses, and at initial presentation:

  • Check height and weight (and monitor regularly afterwards)
  • Measure prolactin levels
  • If considering an antipsychotic, take into account the risk of increased prolactin levels with risperidone and weight gain with olanzapine.
  • If response to an antipsychotic is inadequate, consider adding lithium or valproate but normally avoid valproate in girls and young women.
    • MHRA Drug Safety Update (April 2018): Valproate medicines contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met and only if other treatments are ineffective or not tolerated, as judged by an experienced specialist.
    • The use of valproate in pregnancy is contraindicated for bipolar disorder.

Depression

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

  • Monitor weekly if symptoms are mild and do not need immediate treatment, and offer additional support at home and school
  • If treatment is needed, it should normally be by specialist clinicians (based in at least Tier 3 services).Treat as for adults, but consider a structured psychological therapy in addition to prophylactic medication
  • If this does not produce a response after 4 weeks, consider:
    • adding fluoxetine starting at 10 mg per day, and increasing to 20 mg per day if needed
    • using a different SSRI (sertraline or citalopram) if there is no response to fluoxetine
  • If there is still no response, ask for advice from a specialist
  • For developmentally advanced adolescents, follow the recommendations on managing depression in adults

Long-term treatment of children and adolescents

  • Long-term management should normally be by specialist clinicians (based in at least Tier 3 services).
  • Treat as for adults, but:
    • consider as first line an atypical antipsychotic that is associated with less weight gain and does not increase prolactin levels
    • consider as second line lithium for female patients and valproate or lithium for male patients
      • MHRA Drug Safety Update (April 2018): Valproate medicines contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met and only if other treatments are ineffective or not tolerated, as judged by an experienced specialist.
      • The use of valproate in pregnancy is contraindicated for bipolar disorder
    • give parents and carers support to help the patient maintain a regular lifestyle
    • advise the school or college (with permission of the patient and parents or carers) on managing the patient's bipolar disorder.

Patient focussed resources

 

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