Evidence-based guidelines for treating bipolar disorder

• 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 episode

• 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