Evidence-Based Guidelines for Treating Bipolar Disorder

Overview

This is a Guidelines summary of the British Association for Psychopharmacology's evidence-based guideline on the diagnosis and management of bipolar disorder. It contains recommendations relevant to primary care settings on diagnosis, management, and acute manic and depressive episodes, as well as treatment of alcohol use disorder and treatment in special situations. For the complete set of recommendations refer to the full guideline.

Diagnosis

• Make accurate diagnoses of hypomania, mania and depression:
  • consider identifying core symptoms using:
    • a check list as in DSM-5
    • a patient-completed screening instrument
  • use term 'hypomania' as defined in DSM-5
  • do not dismiss or minimise mood elevation when the cause of disturbed behaviour:
    • personality problems or situational disturbance should be invoked only if mania (or hypomania) is absent
  • in all patients with depression, ask about distinct periods of elated, excited or irritable mood of any duration and a family history of mania
  • diagnosis is only reliable after a clear-cut episode of (hypo)mania
• Possible co-morbidities:
  • assess, monitor and treat:
    • alcohol and/or substance use disorder
    • anxiety disorders
    • borderline personality disorder
• Possible differential diagnoses
  • stimulant drugs (e.g. levodopa and corticosteroids)
  • borderline personality disorder
  • organic conditions, e.g. thyroid disease, multiple sclerosis, or any lesion(s) involving right-sided sub-cortical or cortical areas
• Borderline personality disorder:
  • should not be confused with episodes of mania or depression
  • may be co-morbid with an episodic mood disorder

Pre-pubertal Children

• Defining characteristics: unequivocal euphoria and an episodic course:
  • do not make the diagnosis in children or young people unless there has been a period of prospective longitudinal monitoring by appropriately experienced clinicians taking into account the child or young person’s educational and social functioning
• Possible differential diagnosis:
  • disruptive mood dysregulation disorder (DMDD)

Management

• When mania is diagnosed:
  • always consider admission to hospital or intensive community management
  • offer assessment by a trained psychiatrist
• Risks to the patient and others are from poor judgement and associated actions
  • always try to obtain third party information if in doubt when making a risk assessment
• If in a mixed state or depressed ask about suicidal ideation and plans/means/preparation for suicide
• Assess risk of exploitation, violence and offending
• Carefully document decisions in formulating a care plan
• Establish and maintain a therapeutic alliance:
  • take responsibility for diagnosis, physical examination, investigations and explanation of management plan
  • communicate clearly and honestly
  • listen to what is bothering the patient
  • very disorganised psychotic patients will require assertive management of social needs
• Educate the patient and their family about:
  • the disorder
  • the potential benefits and risks of medication and need to continue it long term
• Enhance treatment adherence:
  • use known tolerability and safety to guide prescribing
  • inform patients about possible side-effects and monitor for emergence
  • prioritise reducing adverse reactions: use different scheduling, alternative formulations or lower doses
• Promote awareness of stressors, sleep disturbance, early signs of relapse, and regular patterns of activity:
  • promote regular patterns of daily activities
    • identify and modify habitual, very irregular patterns
    • consider using diaries or apps to self-monitor mood or activities
  • assess and treat alcohol/drug use and offer advice
  • help the patient and significant others recognise emerging symptoms of manic or depressive episodes
• Evaluate and manage functional impairments:
  • full functional recovery usually takes ≥12 weeks
    • advise patient about withdrawal from work or other responsibilities when necessary
    • discourage major life decisions while in a depressive or manic state
  • manage patient expectations of capacity to work
  • consider needs of patients’ carers and children: provide information about local or national support groups
• Consider physical health in clinical assessment and treatment planning:
  • monitor weight and other relevant risk factors at least annually and offer treatment
  • consult BAP guidelines on management of weight gain and metabolic disturbances associated with psychosis and antipsychotic drug treatment
• Consider the use of alcohol and drugs (including caffeine, tobacco):
  • assess and treat established addictive problems
• Consider risks for adverse outcomes including self-harm, suicide, victimisation, violence and criminality:
  • modifiable risk factors include co-morbid drug and alcohol use disorders and illness severity
• Increase the focus of care planning in women of childbearing potential:
  • address contraception and pregnancy prospectively
  • valproate and carbamazepine are teratogenic
  • risk/benefit of other medicines in pregnancy and breast feeding must reflect risks of relapse as well as their adverse effects
  • very high risk for relapse of bipolar disorder postpartum:
    • consider effective prophylactic treatment

Acute Manic Episodes

• Patients not already taking long-term treatment:
  • severe manic episodes: oral dopamine antagonist (haloperidol, olanzapine, risperidone or quetiapine). Other options:
    • valproate (not for women of childbearing potential)
    • aripiprazole
    • other dopamine antagonists and partial agonists
    • carbamazepine
    • lithium
  • where parenteral treatment required without full patient consent:
    • dopamine antagonists/partial agonists and GABA modulators (benzodiazepines): follow established protocols and use lowest doses necessary
  • less ill, non-psychotic manic patients/hypomania:
    • extrapolate treatment from practice in mania
  • patient preference should guide treatment selection where possible
  • taper and discontinue antidepressants (drugs approved for the treatment of unipolar depression)
  • if initial treatment is successful, consider long-term treatment
• Patients who suffer a manic episode while taking long-term treatment:
  • inadequate symptom control: ensure that highest well-tolerated dose is offered
  • lithium: check serum levels; consider establishing a higher level within the therapeutic range; consider adding dopamine antagonist or partial agonist, or valproate
  • in general, follow the same principles as for a first episode or episode occurring off long-term treatment
  • poor adherence: if associated with adverse reaction, consider dose reduction or more tolerable alternative regimen
  • lithium: may not be indicated long-term if adherence poor
• If symptoms are inadequately controlled with optimised doses of the first-line medicine and/or mania is very severe, add another medicine:
  • lithium or valproate with a dopamine antagonist/partial agonist
  • clozapine in more refractory illness
  • electroconvulsive therapy (ECT) if mania particularly severe/treatment resistant, patient's preference or severe mania during pregnancy
• Mixed features in a manic or hypomanic episode:
  • identify as mixed features rather than a 'mixed episode' (DSM-5)
  • treat as for mania
• Assess contribution of substance use and consider if medically assisted withdrawal is required
• Discontinuation of short-term treatments:
  • plan drug discontinuation in relation to the need for long-term maintenance treatment
  • medicines used only for acute treatment of mania: after full remission of symptoms (≥8 weeks of euthymia), taper dose of over >4 weeks
  • adjunctive medication for symptomatic effect to promote sleep or sedation: discontinue gradually as soon as symptoms improve

Acute Depressive Episodes

• Patients not already taking long-term treatment:
  • consider quetiapine, lurasidone, or olanzapine
  • consider initial treatment with lamotrigine in combination with agents preventing recurrence of mania
  • if considering antidepressants (i.e. drugs for major depressive episode in unipolar illness), co-prescribe with a drug for mania (e.g. dopamine antagonists, lithium, valproate) in patients with a history of mania (e.g. fluoxetine with olanzapine)
  • consider ECT if high suicidal risk, treatment resistance, psychosis, severe depression during pregnancy or life-threatening inanition
  • where depressive symptoms less severe: lithium
  • additionally: family-focused, cognitive behaviour therapy or interpersonal rhythm therapy
• Patients who suffer a depressive episode while taking long-term treatment:
  • ensure current choice of long-term treatments is likely to protect from manic relapse (e.g. lithium, valproate, dopamine receptor antagonist/partial agonist drugs)
  • ensure adequate doses of medicines, serum lithium levels within therapeutic range
  • address current stressors
  • if patient fails to respond to optimisation of long-term treatment, initiate treatment as above (or as for treatment-resistant depression, below)
• Choice of drug for a depressive episode:
  • monotherapy with antidepressants may increase risk of switch to mania or mood instability during treatment
  • dual-action monoamine re-uptake inhibitors (venlafaxine, duloxetine, amitriptyline and imipramine) carry a greater risk of precipitating a switch to mania than single action drugs (especially selective serotonin re-uptake inhibitors)
  • antidepressant drugs appear unlikely to induce mania when used in combination with a drug for mania
  • antidepressant as monotherapy in bipolar II disorder: any increase in dose should be gradual; be vigilant for early management of any adverse reactions (e.g. hypomania, mixed states or agitation)
  • lamotrigine: effective in bipolar I and suitable for bipolar II disorder
  • if any treatment successful for depressive episode, consider long-term treatment
• Consider tapered discontinuation of antidepressant drugs after as little as 12 weeks' full remission of symptoms:
  • longer treatment justified if patients relapse on withdrawal
• Treatment of resistant depression:
  • consider ECT
  • manage augmentation strategies as in unipolar patients; ensure adequate anti-manic cover with lithium, valproate, or a dopamine antagonist/partial agonist

Long-term Treatment

• Prevention of new episodes:
  • consider long-term treatment following a single severe manic episode
  • consider a wider package of treatment with enhanced psychoeducation, motivational, and family support, especially in early stages of illness
  • patient has accepted treatment for several years and remains very well: advise continuing indefinitely, as high risk of relapse
• Options for long-term treatment:
  • continuous rather than intermittent treatment with oral medicines preferred
  • optimum long-term treatment strategy is not established
  • acute stressor imminent or present, early symptoms of relapse, or anxiety prominent: short-term add-ons (e.g. GABA modulators or dopamine antagonists/partial agonists):
    • consider supplying prospectively to patients
  • higher doses of long-term treatments may be effective instead of add-ons
• Choice of long-term medicines:
  • consider lithium as initial monotherapy
  • if lithium ineffective, poorly tolerated or poor adherence: valproate, dopamine antagonists/partial agonists
  • if a medicine led to prompt remission from the most recent depressive or manic episode, consider its long-term use:
    • consider lithium as a better alternative to dopamine agonists
  • alternative against manic relapse: carbamazepine (or oxcarbazepine)
  • if prophylaxis against recurrence of mania is required and adherence to oral medication is erratic or injection preferred:
    • consider long-acting (‘depot’) formulations
  • consider lamotrigine and quetiapine as monotherapy in bipolar II disorder:
    • in bipolar I disorder, lamotrigine usually requires combination with an anti-manic long-term
• Failure to respond to monotherapy, continuing sub-threshold depressive symptoms/relapses:
  • consider long-term combination treatment:
    • predominantly manic: combine predominantly anti-manic agents (e.g. lithium, valproate, dopamine antagonist or dopamine partial agonist)
    • predominantly depressive: combine lithium, lamotrigine, quetiapine, lurasidone, or olanzapine
    • refractory mania: consider continuation of clozapine if effective
    • responsive to ECT during an acute episode, but poor on oral agents: consider maintenance ECT
    • consider adjunctive psychotherapy
• Rapid cycling:
  • identify and treat contributing conditions (e.g. hypothyroidism or alcohol/drug use)
  • taper and discontinue antidepressants
  • combinations of medicines may be required
    • discontinue treatments ineffective after evaluation ≥6 months
• Discontinuation of long-term treatment:
  • risk of relapse remains, even after years of sustained remission
  • make an informed assessment of the potential dangers
  • taper over ≥4 weeks
  • discontinuation of medicines does not imply withdrawal of services to patients
• Specific psychosocial interventions:
  • may enhance care and reduce risk of relapse
  • structured psychoeducation appears to be key ingredient
  • more successful with patients early in illness course
  • user groups can provide useful support and information

Treatment of Alcohol Use Disorder

• Offer naltrexone or nalmefene as part of a behavioural programme
• Offer acamprosate if naltrexone has not been effective to help patients remain abstinent

Treatment in Special Situations

• Children and young people:
  • for mania:
    • consider aripiprazole or refer to adult recommendations
    • other options: olanzapine, quetiapine and risperidone
  • for moderate to severe bipolar depression:
    • consider medicines and psychological treatments as recommended for adults
  • refer to BNF for Children to modify doses and be aware of increased potential for adverse reactions and effects
• Elderly
  • consider lower treatment doses and titrate carefully
• Women and pregnancy
  • see management section