Overview of main concepts related to bipolar disorder
Bipolar disorder affects 2.8 % of the adult population. Bipolar I affect men and women equally while bipolar II affects more women than men. Age of onset is late adolescence or early adulthood. The average time to correct diagnosis is 10 years. It is a chronic illness with remissions and exacerbations even on medication (50% of the time the patient is unwell).
- Bipolar II more time ‘unwell’
- Bipolar II – predominant mood state is depression
- Bipolar I more time hypomanic/manic than Bipolar II
- 60% of patients have significant and chronic interpersonal and occupational difficulties
- Completed suicide rate is ~10 %
- Suicide attempts: 30%-50%
- Increased risk of suicide attempts in mixed depressive states.
Screening tool
WHIPLASHED screening tool for bipolar depression or the presence of bipolarity
and assists to differentiate bipolar from unipolar depression:
W - Worse or ‘wired’ when taking antidepressants. Failed trials. Switching on AD
H - Hypomania, hyperthymic temperament
I - Irritability and mixed features during the presenting episode of depression
P - Psychomotor retardation
L - Loaded family history
A - Abrupt onset and/or termination of depressive bouts
S - Seasonal or postpartum pattern of depression
H - Hyperphagia and hypersomnia
E - Early age at depression onset (younger than 25 years)
D - Delusions, hallucinations, or other psychotic features appear to be more common in bipolar disorder.
Making a diagnosis of a bipolar mixed mood state
Types of mixed states:
- Depressed type with hypomanic/manic features
- Hypomanic/manic type with depressed features.Risk of untreated bipolar depressive or mixed states:
- High risk of suicidal ideation (>70% attempts) during mixed and depressed episodes of bipolar disorder
- Mixed episodes are particularly high risk for suicide attempts
- Overdose is the most common method of suicide (caution with certain medications)
- Significant functional and cognitive impairment is associated with untreated lengthy episodes of bipolar disorder.
Management of bipolar depression and mixed mood states
Follow the general treatment principles and assess:
- Medication status
- Risk
- Setting of treatment
- Laboratory investigations
- Substance use
- Past response to agents
- Recent discontinuation of agents
- Consider ECT (suicide risk, psychotic depression, catatonic).
First-line agents for bipolar depression
Monotherapy: Quetiapine 300-600mg (evidence for 150 mg +)
Lithium (target 0.8-1.2meq/l)
Lamotrigine (target >200mg – need to go up slowly 25mg every two weeks).
Adjunct agents:
- Quetiapine
- Lithium
- Lamotrigine
If depressed on an antidepressant, switch or stop the antidepressant (be careful with venlafaxine), taper and cross-titrate.
- Alternative first-line agent/second-line treatments. Don’t switch lamotrigine as it needs time to work
- Add on or switch treatment – second line agents
- Monotherapy – valproate
- SSRI (adjunct)
- Bupropion (adjunct)
- Olanzapine + fluoxetine
- Monotherapy – valproate.
Alternative third-line treatment:
- Aripiprazole (adjunct)
- Carbamazepine (mono)
- Ketamine IV (adjunct)
- Levothyroxine (adjunct)
- Olanzapine (mono).
Agents not recommended for treatment of bipolar depression:
- Antidepressant monotherapy
- Aripiprazole monotherapy
- Ziprasidone monotherapy
- Gabapentin
- Risperidone.
Expert consensus
According to the International Society for Bipolar Disorders (ISBD) Antidepressant Task Force recommendations for the use of antidepressants in bipolar depression: Mood stabilisers or atypical antipsychotics should be considered as first-line treatment for bipolar depression.
Antidepressants should be used with caution in bipolar depression, especially in patients with a history of switching to mania or hypomania during antidepressant treatment. The potential risks and benefits of antidepressant treatment should be considered in individual patients.
Patients should be closely monitored for manic or hypomanic symptoms during antidepressant treatment, particularly during the first few weeks or after dosage adjustments. A low-dose antidepressant in combination with a mood stabiliser or atypical antipsychotic may be considered instead of using an antidepressant as monotherapy. Antidepressant treatment should be discontinued in patients who do not respond adequately after four-six weeks, or who experience significant adverse effects or switch to mania or hypomania.
Non-pharmacological interventions such as psychotherapy or light therapy may be considered adjunctive treatment for bipolar depression.
Pharmacological treatment of mixed episodes
Distinguish mixed states from both mania and agitated depression. Taper and cease medications with mood elevating properties, especially those that may induce inter-episode switching. Antidepressants can worsen or induce rapid cycling and are thus not recommended. Lithium may have reduced efficacy for treating mixed states.
Treatment options include:
- Olanzapine
- Quetiapine or valproate as monotherapy
- Olanzapine and fluoxetine in combination
- Valproate in combination with olanzapine.
Important discussions with your patient
- Adherence
- Collaborative, understanding reasons for non-adherence, 50% non-adherence rate
- Educate on side effects
- Educate on treatment withdrawal – 50-90% of lithium withdrawal relapse within five months
- Risks for suicide and development of mixed mood states
- Management of comorbidities.
