Bipolar and related disorders

• Bipolar and related disorders are defined by episodes of mania or hypomania alternating, usually, with episodes of depression; cyclothymia sits at the milder, chronic end of the spectrum.
• Bipolar I disorder requires at least one full manic episode (it may occur without any depressive episode). Bipolar II disorder requires at least one hypomanic episode plus one major depressive episode, and no full manic episode. Cyclothymic disorder is chronic subthreshold mood instability.
• A full manic episode lasts at least one week (or any duration if hospitalisation is needed) and causes marked impairment or psychosis; hypomania lasts at least four days and stays below the level that disables the person or needs admission.
• First-line long-term treatment is lithium, monitored by blood levels; alternatives and adjuncts include quetiapine, valproate, lamotrigine and other antipsychotics. Bipolar depression is treated with quetiapine, lamotrigine, lithium or selected combinations, not antidepressant monotherapy as a default.
• Suicide risk is much higher than in the general population; risk assessment is part of every contact, and lithium itself reduces suicide risk.

By the end of this page you should be able to:

1. Distinguish bipolar I, bipolar II and cyclothymic disorder, and name the specifiers and the mixed features concept.
2. Recognise mania, hypomania and mixed states from the history and mental state examination, using the DIG FAST symptom group.
3. List the differential diagnoses of a first episode and explain which features separate them.
4. Describe the investigations and screening tests used, and their cut-offs or normal ranges.
5. Choose evidence-based, phase-appropriate treatment, with doses, levels and monitoring for lithium, valproate, lamotrigine and antipsychotics.
6. Assess suicide risk and manage bipolar disorder in pregnancy, children and older adults, including the hazards of valproate and lithium.
7. Set out the short- and long-term prognosis and the psychosocial measures that reduce relapse.

Bipolar I disorder is present once a person has had one manic or mixed episode, even if no depressive episode has ever occurred. Bipolar II disorder requires at least one hypomanic episode and at least one major depressive episode, and no manic episode ever. Cyclothymic disorder means numerous periods of hypomanic symptoms and depressive symptoms over at least two years, without meeting full criteria for a manic, hypomanic or major depressive episode.

Current classification also includes "other specified bipolar and related disorder" and "unspecified bipolar and related disorder", and episodes that are judged to be due to a medical condition or to a substance or medication. Two international systems now align closely on these categories: the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and the International Classification of Diseases, eleventh edition (ICD-11).^[1]

Specifiers refine the course and features of the illness: anxious distress, mixed features, rapid cycling, melancholic or atypical features, psychotic features, catatonia, peripartum onset, seasonal pattern, severity and remission. Mixed features has replaced the older idea of a discrete "mixed episode": a person can have features of the opposite pole during a manic, hypomanic or depressive episode. In DSM-5 mixed features is a specifier, while ICD-11 keeps "mixed episode" as a separate episode type.^[1]

Lifetime prevalence figures differ by method and setting, so treat them as ranges rather than single numbers. A large cross-national survey found a lifetime prevalence of bipolar spectrum disorders of about 2.4%, made up of about 0.6% bipolar I disorder and 0.4% bipolar II disorder, with the rest subthreshold.^[4][1] Other pooled estimates put lifetime prevalence at about 1.1% for bipolar I disorder and 1.6% for bipolar II disorder. If both types are combined, worldwide prevalence is about 1% to 3%.^[4][5] Bipolar I disorder is found in about 0.87% to 1.0% of people in some North American samples and about 0.6% in the 11-country survey; bipolar II disorder in about 0.4% to 0.67%.^[1][4]

The condition is roughly equally common in men and women, although some studies find more manic episodes and bipolar I disorder in men and more bipolar II disorder in women.^[4] It is not restricted to high-income settings: lifetime prevalence in African countries has been reported between 0.1% and 1.8%.^[4]

Onset is usually in late adolescence or early adulthood, with a mean in the early twenties and a range of about 20 to 30 years. Some population studies describe two peaks, at 15 to 24 years and at 45 to 54 years.^[4] About 16% of people treated for depression turn out to have a bipolar disorder.^[5]

Suicide is one of the leading causes of death. Approximately 6% to 7% of identified patients die by suicide, a higher fatality rate than in the general population, and a recent task force estimate gives 164 suicide deaths per 100,000 patients with bipolar disorder per year against 10 per 100,000 in the general population.^[2][6] Around 43% report suicidal thoughts, 21% a plan and 16% an attempt in the past year.^[2]

Bipolar and related disorders are multifactorial. They do not follow a simple inheritance pattern, but heritability is strong: monozygotic twin concordance is about 40% to 70% and the lifetime risk in a first-degree relative is about 5% to 10%, roughly seven times the population risk. Relatives are, however, more likely to develop unipolar depression than bipolar disorder, so the genetic risk crosses diagnostic boundaries.^[4]

Genome-wide studies have found many loci of small effect, including associations near calcium-channel genes such as CACNA1C. These small individual effects mean that environment matters too.

Reported risk factors include:

• Childhood adversity, which a meta-analysis found about 2.6 times more common overall (and emotional abuse about four times more common) in people who later develop bipolar disorder than in controls, and which is linked to earlier onset, more episodes, substance use and suicide attempts.^[4]
• Cannabis use, which in prospective studies roughly doubles to triples the risk of new manic symptoms and shows a dose-response relationship in some cohorts; the association may be causal or reflect self-medication and shared vulnerability.^[4]
• Perinatal infection with Toxoplasma gondii, which shows a consistent association with bipolar disorder in meta-analyses.^[4]
• Obstetric and prematurity factors, where the evidence is weaker and inconsistent.^[4]
• Stressful life events, which commonly precede relapse and are implicated in onset, although the causal question is not settled.^[4]
• Medical comorbidity, including obesity, asthma, irritable bowel syndrome and migraine, and substance use disorders, which occur in up to about 45% of clinical samples.^[1][4]

No modifiable risk factor is strong enough on its own to prevent or cause the illness, and most are shared with other mental disorders. Where a patient presents with a first manic-like episode after middle age, organic causes such as cerebrovascular disease, frontal lobe lesions or hyperthyroidism should be actively excluded.

The cause of bipolar disorder is not settled, and several models are held together rather than as a single answer.^[5]

• Neurotransmitter and ion-channel models: manic and depressive states have been linked to altered dopamine signalling and to calcium signalling inside neurons. Many mood stabilisers and antipsychotics act on ion channels or dopamine receptors.
• Cellular energy models: mitochondrial dysfunction and altered cerebral energy metabolism have been proposed, with supporting genetic and animal-model evidence; lithium and some antipsychotics may partly work through these pathways.
• Neuroplasticity models: neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and inflammatory signals such as interleukin-6 are altered, particularly with early adversity and repeated episodes.
• Circadian and sleep models: sleep loss can trigger mania, and social-rhythm stabilisation helps prevent recurrence; many patients have marked circadian disruption.

A useful summary for the bedside: repeated mood episodes, and anything that lowers sleep or raises stimulation, make further episodes more likely, possibly through "kindling" in limbic circuits. Mania is not simply "too much happiness" but a state of dysregulated energy, sleep, thought and behaviour.

Mania is an abnormal, persistent, pervasive elevation, expansiveness or irritability of mood, accompanied by increased energy or activity, most of the day, nearly every day. Hypomania is similar but milder and shorter. Depressive episodes are the mirror image and dominate the illness over a lifetime.

A classic mnemonic for mania is DIG FAST, each letter a clinical feature:

• Distractibility
• Indiscretion or poor judgement (spending, sex, risky plans)
• Grandiosity
• Flight of ideas (racing thoughts)
• Activity increased (goal-directed or disorganised)
• Sleep decreased (less need, feeling rested)
• Talkativeness or pressured speech

These features are not DSM wording; they are a memory aid. The episode must also represent a clear change from the person's usual self and be observable by others.

For a manic episode, the mood and energy change lasts at least one week, or any length if hospitalisation is required, and is severe enough to cause marked impairment, to require hospital care, or to include psychotic features. At least three of the above features are needed (four if the mood is only irritable).^[6][2]

For a hypomanic episode, the change lasts at least four days, is clearly different from usual functioning, and is noticeable to others, but stays below the level that disables the person, needs admission or brings psychosis.^[6][3]

For a major depressive episode, at least five of the standard depressive symptoms, including depressed mood or loss of interest, are present for two weeks or more, cause impairment and are not better explained by another condition.^[5]

Rapid cycling means four or more mood episodes (manic, hypomanic, mixed or depressive) within 12 months, with partial or full remission or a switch in polarity between episodes. It occurs in a minority of patients and makes the illness harder to treat.^[5]

Mixed features mean that during a manic, hypomanic or depressive episode the person also has several symptoms of the opposite pole most days; for example, a patient with mania who is also despairing, agitated and suicidal, or a depressed patient who is restless, racing and grandiose. Such presentations carry particularly high suicide risk.^[1][2]

• A first presentation is often depression. Look for a low threshold to suspect bipolar disorder in depression that begins before the age of 25, that recurs (five or more episodes), that has psychotic or atypical features, that follows an antidepressant switch into hypomania or mania, or that occurs postpartum.^[1][6]
• Patients may not experience hypomania as illness and may under-report it, especially when depressed. Collateral history from family is essential.
• A third or more of people with bipolar disorder also use substances, which can mimic or provoke mania.^[2]

In a manic or hypomanic state you may find:

• Appearance and behaviour: increased energy, over-familiarity, disinhibition, flamboyant dress, pacing, restlessness, poor self-care in more severe cases.
• Speech: rapid, loud, difficult to interrupt, increased quantity, punning or rhyming.
• Thought: flight of ideas, grandiose or persecutory content, sometimes delusions or hallucinations in mania.
• Mood: elevated, irritable or labile; the person often lacks insight and feels unusually well.
• Cognition and memory: generally preserved between episodes; thinking is fast and easily distracted during the episode.
• Insight: usually poor in mania; the patient may not see any problem.

In depressive episodes the findings are those of a major depression, and the safety assessment is paramount. A normal examination between episodes does not exclude bipolar disorder.

There is no physical sign specific to bipolar disorder. Assess weight, body-mass index, blood pressure, cardiovascular and metabolic status, thyroid, and signs of self-neglect or of substance use. Abnormal movements, focal neurological signs or cognitive change in an older person should raise suspicion of an organic cause.

Suicide is one of the leading causes of death in bipolar disorder, so risk is assessed at every contact, including during euthymic periods. Suicidal ideation is reported by around 43%, a plan by 21% and an attempt in the past year by 16% of patients; about 6% to 7% of identified patients eventually die by suicide, a higher fatality rate than in the general population. ^[1][2]

Risk is increased by depressive or mixed polarity, hopelessness, psychomotor agitation, substance use, comorbid anxiety or personality disorder, past attempts, early onset, rapid cycling, childhood adversity, and the periods during and after hospitalisation. Lithium, and to a lesser extent anticonvulsants, is associated with reduced attempts and deaths; antidepressants have limited supportive data. Because self-poisoning is the most common method, the quantity of medication dispensed at once should be limited during high-risk periods and the lethality of each drug considered: lithium is among the agents least lethal in overdose, while opioids, antipsychotics, benzodiazepines and certain anticonvulsants are more so. ^[1][2]

Practical management: ask directly about thoughts, plans, means and intent; agree an individualised crisis plan with warning signs, triggers, coping steps, emergency contacts and medication actions; if access to means is a concern, restrict them; recheck after any change in mood, sleep, loss, or hospitalisation.

The main risk is to label a first manic episode as schizophrenia, or a bipolar depression as unipolar depression. Both errors are common and delay effective treatment.^[1][6]

There is no laboratory test that diagnoses bipolar disorder. Investigations serve three purposes: to rule out organic causes and comorbidity, to establish a baseline before treatment, and to monitor treatment.

Bipolar disorder is a clinical diagnosis based on longitudinal history, not on a single cross-sectional interview. DSM-5 and ICD-11 criteria are copyright texts and are summarised here, not quoted.

• Bipolar I disorder: at least one lifetime manic (or mixed) episode. A major depressive episode is common but not required.
• Bipolar II disorder: at least one lifetime hypomanic episode and at least one major depressive episode, with no manic episode.
• Cyclothymic disorder: at least two years (one year in children and adolescents) of numerous periods of hypomanic-level and depressive symptoms that do not meet full episode criteria.

Specifiers modify the diagnosis and guide treatment: anxious distress, mixed features, rapid cycling, melancholic or atypical features, psychotic features, catatonia, peripartum onset, seasonal pattern, severity and remission. Only about 5% of people with bipolar II disorder later develop bipolar I disorder, supporting its stability as a subtype.

Management is phase-specific and guided by the evidence-based recommendations of the current editions of NICE (CG185, last updated September 2025), CANMAT/ISBD 2018 and the APA practice guideline (second edition, 2002, now legacy). NICE and CANMAT/ISBD 2018 are the principal current sources here; the APA has not issued a newer bipolar disorder guideline. NICE applies its recommendations to bipolar I, bipolar II, mixed affective and rapid cycling disorders.

General measures: provide a calm, low-stimulation environment, reduce decisions and activity, protect sleep, involve family where possible, and assess risk continuously.^[2]

• If the person is not taking a mania treatment, offer haloperidol, olanzapine, quetiapine or risperidone, taking into account preference and clinical context, with monitoring as set out in the Medication section. Quetiapine is titrated from 100 mg on day 1 to 300 mg by day 3, reaching a recommended range of 400 to 800 mg per day for mania (maximum 800 mg per day).^[2][9]
• If the first antipsychotic is ineffective or poorly tolerated, including rapid weight gain, try an alternative from the same list, then consider adding lithium. If lithium is added to an antipsychotic and still fails, valproate may be added instead, subject to the MHRA valproate restrictions. Lithium may be used as adjunctive treatment for acute mania in NICE guidance, with levels optimised to 0.8 to 1.2 mEq per L. If the person is already taking lithium, check the plasma level to optimise treatment. If already taking valproate, review adherence and consider increasing the dose.^[2][1][3]
• If the presentation is a mixed affective state, treat on the mania pathway and monitor closely for emerging depression. Do not use lamotrigine for mania.

• Offer psychological treatment for bipolar depression: either a structured bipolar-specific psychological intervention with a published manual, or cognitive behavioural, interpersonal or behavioural couples therapy; monitor mood for emerging hypomania.^[2]
• If the person is not taking a mood-stabilising drug, NICE recommends fluoxetine combined with olanzapine, or quetiapine monotherapy. Olanzapine alone or lamotrigine alone may be considered if preferred. For quetiapine, the bipolar depression dose is 50 mg on day 1, 100 mg on day 2, 200 mg on day 3 and 300 mg from day 4, with a recommended dose of 300 mg per day; there is little added benefit at 600 mg per day.^[2][9]
• If already taking lithium (level 0.8 to 1.0 mEq per L in maintenance, but higher allowed during an episode), optimise lithium first; if the level is already at target, add fluoxetine with olanzapine or quetiapine, or olanzapine or lamotrigine if preferred.
• If already taking valproate, review the dose and adherence; if there is limited response, add either fluoxetine with olanzapine or quetiapine, or consider switching away from valproate. Follow the MHRA valproate restrictions.^[2][7]
• CANMAT/ISBD 2018 first-line options for bipolar I depression are quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. Adjunctive antidepressants may be used, but evidence for their efficacy in bipolar depression is limited and the risk of treatment-emergent switch is higher in bipolar I than in bipolar II disorder. For bipolar II depression, expert consensus recommends quetiapine first, then lithium, lamotrigine or an antidepressant, and expert reviews judge the overall switch risk on antidepressant treatment to be about 12%, with hypomania (not mania) the usual outcome.
• Electroconvulsive therapy is an option for severe or life-threatening mania or depression when other treatments have not worked.^[2]

• After every episode, discuss long-term treatment with the patient, family and carers, including relapse risk, pregnancy wishes and monitoring.^[2]
• Lithium is the first-line long-term pharmacological treatment. CANMAT/ISBD 2018 also lists lithium, quetiapine, divalproex, lamotrigine, asenapine and aripiprazole (alone or combined) as first-line maintenance options.^[1][2]
• If lithium is ineffective, poorly tolerated or refused, consider an antipsychotic such as asenapine, aripiprazole, olanzapine, quetiapine or risperidone; if one fails, try another; if that fails, consider valproate with an antipsychotic or lithium. ^[2]
• For maintenance, quetiapine is used at 400 to 800 mg per day, usually continuing the dose on which the patient was stabilised.^[9]
• Lamotrigine is used for maintenance only, at a target of 200 mg per day, or 100 mg per day with valproate and 200 to 400 mg per day with an enzyme inducer, with slow titration to reduce rash risk. It is not used for acute mania. ^[8][2]
• Antidepressants started during depression are usually withdrawn once stable, because ongoing treatment drives switches and rapid cycling.
• Psychological care for relapse prevention includes psychoeducation, family intervention, structured relapse-prevention work, interpersonal and social rhythm therapy, and supporting regular routines and sleep.^[2]
• When stopping long-term medication, reduce it gradually and monitor for two years, with a written relapse and crisis plan, agreed triggers and emergency contacts. ^[2]

Lithium is the foundational mood stabiliser and reduces suicide risk. There is no fixed dose: it is titrated to a serum level.

• Adults and children over 30 kg: 300 mg three times daily, or 8 mEq (5 mL) of lithium solution three times daily, is a typical starting point; titrate by increasing roughly 300 mg (or 8 mEq) every three days.
• Acute manic or mixed episodes (age 7 and older): target a serum lithium concentration of 0.8 to 1.2 mEq per L (mmol per L).
• Maintenance (age 7 and older): target 0.8 to 1.0 mEq per L.
• Lithium-naive or older patients: an initial level of 0.6 to 0.8 mmol per L is often used in practice, raised to 0.8 to 1.0 if response is suboptimal; levels are generally based on samples drawn 12 hours after the last dose. Some pathways use lower targets in patients aged 65 or older. This is a point where guidelines genuinely differ; use local practice and the specialist target. ^[2][3]
• Children 20 to 30 kg: 300 mg twice daily (or 8 mEq twice daily), titrated more slowly.

Sampling and early monitoring

• Samples are drawn 12 hours after the last dose. Start checking after 3 days and then regularly until the patient is stabilised. Check 1 week after starting and 1 week after every dose or formulation change. ^[3]
• Once stable, check at least every 3 months in the first year, then every 3 to 6 months depending on local guidance; more often (at least every 3 months) if the patient is 65 or older, takes interacting drugs, has impaired renal or thyroid function or raised calcium, has poor adherence or symptom control, or had a last level of 0.8 or more. ^[3]
• Also recheck after a marked change in physical activity or any concomitant illness, and at any suggestion of toxicity.

Baseline before starting (for all lithium)

Renal function, vital signs, serum electrolytes including sodium and potassium, thyroid function and calcium, full blood count, body weight or BMI, and an ECG if cardiovascular disease or risk factors are present. Pregnancy status and potential in women of childbearing age must be assessed first. ^[2][3]

Monitoring during treatment (every 6 to 12 months, or as clinically indicated)

• Renal function and urea and electrolytes at least twice a year, more often if impaired.
• Thyroid function at baseline, at 3 months, then every 6 to 12 months.
• Calcium at baseline and periodically.
• Weight or BMI, blood pressure and full blood and metabolic checks at least every 12 months in primary care, with lithium users included in the annual physical health check. ^[2][3]

Toxicity

• The toxic concentration (at or above 1.5 mEq per L) is close to the therapeutic range (0.8 to 1.2). Some patients show toxic signs at therapeutic levels, and older people are more sensitive. ^[3]
• Neurological signs range from fine tremor, lightheadedness, weakness and lack of coordination, through giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus and slurred speech, to clonus, confusion, seizure, coma and death. Gastrointestinal, cardiac (QT prolongation, myocarditis), renal (concentrating defect, nephrogenic diabetes insipidus) and respiratory manifestations also occur. There is no specific antidote. ^[3]
• Risk is increased by concurrent febrile illness, drugs that raise lithium levels (diuretics, non-steroidal anti-inflammatory drugs, angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers, metronidazole), acute ingestion, impaired renal function, dehydration or sodium loss, significant cardiovascular disease and electrolyte disturbance. ^[3]
• Patients should maintain a normal diet with adequate salt and a fluid intake of roughly 2500 to 3000 mL per day, especially during initial stabilisation. ^[3]
• If toxicity is suspected, withhold lithium, check an urgent serum level and renal function, and seek specialist help; serial levels matter because lithium distributes slowly. Consider intravenous fluids to increase renal elimination and expert advice about haemodialysis in severe cases.
• Long-term lithium can cause nephrogenic diabetes insipidus (consider amiloride), chronic tubulointerstitial kidney damage, hypothyroidism and hyperparathyroidism. Thyroid or parathyroid complications are treatable without stopping lithium if needed. ^[3]
• Encephalopathic syndrome can occur with lithium plus an antipsychotic; monitor cognitive function. ^[3]

Practical prescribing points for lithium

• Avoid or reduce lithium in severe renal impairment (creatinine clearance under 30 mL per minute); use lower starting doses and closer monitoring with clearance of 30 to 89 mL per minute. ^[3]
• Beware interactions with diuretics, non-steroidal anti-inflammatory drugs, angiotensin system blockers, metronidazole, carbamazepine and antipsychotics; counsel about over-the-counter ibuprofen, dehydration and intercurrent illness. ^[3]
• Polyuria and thirst are common, particularly early; educate the patient and distinguish benign polydipsia from nephrogenic diabetes insipidus.

Valproate is a first-line treatment for acute mania and is also used for maintenance and as an adjunct in bipolar depression. ^[1][2] For acute mania it is started at 750 mg per day in divided doses, raised rapidly to the lowest dose producing a clinical response, guided by trough plasma levels of 50 to 125 micrograms per mL, up to 60 mg per kg per day. ^[7]

Safety

• Hepatotoxicity, sometimes fatal, is highest in children under two years, in mitochondrial (POLG-related) disorders and in urea cycle disorders; valproate is contraindicated in the last two. Monitor liver function, especially in the first six months. ^[7]
• Pancreatitis can occur. Abdominal pain, nausea or vomiting on valproate should be treated as possible pancreatitis until excluded. ^[7]
• Thrombocytopenia is dose-related; women are more affected above 110 micrograms per mL, men above 135 micrograms per mL. Check complete blood count and coagulation, especially before surgery or in pregnancy. ^[7]
• Hyperammonaemia can cause encephalopathy, worsened by topiramate. Consider ammonia measurement with unexplained lethargy or vomiting. ^[7]
• Drug interactions: enzyme inducers such as carbamazepine and phenytoin can double valproate clearance; valproate can raise levels of lamotrigine, amitriptyline and others; carbapenems can reduce valproate concentrations to subtherapeutic levels. ^[7]
• The risk of suicidal thoughts or behaviour is increased by antiepileptic drugs in general. ^[7]
• Hypothermia and somnolence in the elderly are recognised hazards; start lower and titrate more slowly in older patients. ^[7]

Monitoring valproate

Check liver function, full blood count and (in women) pregnancy status before starting. The commonly cited therapeutic range for most patients is 50 to 100 micrograms per mL; response in acute mania trials was guided by 50 to 125 micrograms per mL. ^[7]

Valproate restrictions (MHRA/NICE, 2024-25 update)

• Do not start valproate for the first time in people under 55, male or female, unless two specialists independently agree and document that there is no other effective, tolerated treatment. ^[2]
• Valproate is contraindicated in women and girls of childbearing potential unless other options are ineffective or intolerable, after full discussion of fetal risks, with pregnancy prevention measures where appropriate. ^[2][7]
• Boys and men should be advised to use effective contraception throughout treatment and for 3 months after stopping valproate; men planning a family within a year should be advised of potential fertility risks. ^[2]
• For migraine prophylaxis, valproate is contraindicated in pregnant women and in women of childbearing potential not using effective contraception; in epilepsy and bipolar disorder it is avoided in pregnancy unless other treatments have failed. ^[7]

Lamotrigine is a first-line option for bipolar I depression and for maintenance (CANMAT/ISBD 2018), but it is not used for acute mania. ^[1][8][2]

• Target maintenance dose: 200 mg per day. With valproate, which reduces clearance, the target is 100 mg per day. With an enzyme inducer such as carbamazepine, phenytoin or phenobarbital, or with rifampin, the target is 200 to 400 mg per day. ^[8]
• Titrate slowly to reduce rash: with valproate, 25 mg every other day for two weeks, then 25 mg daily for two weeks, 50 mg, 100 mg and then 100 mg daily. Without valproate or an inducer: 25 mg, 50 mg, 100 mg, 200 mg and then 200 mg daily over seven weeks. With an inducer: 50 mg, 100 mg, 200 mg, 300 mg and up to 400 mg daily. ^[8]
• If valproate is stopped, double the lamotrigine dose over two weeks; if an inducer is stopped, halve it. ^[8]
• Serious rash (including Stevens-Johnson syndrome) occurs in about 0.08% of adults in bipolar trials, more often with valproate combination. Stop at the first sign of rash unless clearly not drug-related; the risk is lower with slow titration. ^[8]

Second-generation antipsychotics are first-line across all phases in CANMAT/ISBD 2018: aripiprazole, asenapine, cariprazine, olanzapine, paliperidone, quetiapine and risperidone for mania; lurasidone, olanzapine-fluoxetine combination and quetiapine for bipolar depression; and several for maintenance. They are preferred when lithium is ineffective, poorly tolerated or refused, and for mixed features, comorbid substance use and in many pregnant patients. ^[1][2]

Practical points common to all antipsychotics:

• Baseline weight or BMI, pulse, blood pressure, fasting glucose or HbA1c and lipid profile before starting. ^[2]
• ECG if the drug summary requires it or if there are cardiac risk factors, family history or inpatient admission. ^[2]
• Weekly weight for the first 6 weeks, then at 12 weeks, with glucose and lipids at 12 weeks; switch or stop if rapid weight gain or intolerable side effects. ^[2]
• For bipolar mania, quetiapine (400 to 800 mg per day) or quetiapine extended-release (300 mg on day 1, 600 mg on day 2, then 400 to 800 mg) is titrated quickly and continued at the stabilising dose. ^[9]

Mixed features are treated on the mania pathway with close monitoring for emerging depression. No agent met the threshold for first-line treatment of DSM-5 mixed presentations in the dedicated CANMAT mixed-features review; asenapine, cariprazine, divalproex, aripiprazole, olanzapine-combination and carbamazepine carry evidence in various mixed states, while quetiapine, lithium and olanzapine are used for maintenance. Practically the approach is an antipsychotic, lithium or valproate, without antidepressant monotherapy. ^[1][2]

Rapid cycling is managed with the same interventions as other types, because there is no strong evidence that it needs a different approach. The emphasis is on treating depression vigorously while avoiding switches into mania, plus close monitoring and adherence support. ^[1][2][5]

• Suicide and self-harm, the most serious complication; risk is contributed to by mixed features, depressive polarity, substance use, comorbid personality disorder, past attempts and recent hospitalisation. ^[1][2]
• Substance use disorders, in up to 45% in clinical samples, worsen outcomes, increase hospitalisation and suicide risk. ^[1][4]
• Psychiatric comorbidity: anxiety disorders in 24% to 56%, personality disorder in about 42%, attention deficit hyperactivity disorder in 10% to 20%. ^[1]
• Cardiovascular and metabolic disease, aggravated by antipsychotics, lithium and lifestyle; cardiovascular disease is the leading cause of death in people with bipolar disorder. ^[5]
• Cognitive and functional impairment, especially after many episodes or with early adversity.
• Treatment-related complications: lithium toxicity and nephrogenic diabetes insipidus, chronic kidney damage, hypothyroidism; valproate hepatotoxicity, pancreatitis, teratogenicity, thrombocytopenia; lamotrigine rash; antipsychotic metabolic, extrapyramidal and cardiac effects; antidepressant-emergent switch.
• Social consequences: loss of relationships, employment and financial stability through manic spending and behaviour, and stigma.
• Repeat mixed or rapid-cycling course, associated with treatment resistance and early adversity. ^[4][5]

Left untreated, manic and depressive episodes eventually resolve, but most patients relapse without treatment, and the interval between episodes shortens over time. ^[5] Depression dominates the long-term course and is the main source of disability and suicidality. The aim of treatment is not simply to end episodes but to prevent recurrence, stabilise sleep and routines, and preserve functioning and cognition.

Favourable factors include good early response to lithium, strong adherence, stable psychosocial support and preserved insight. Unfavourable factors include early onset, mixed features, rapid cycling, substance use, comorbid personality disorder, many prior episodes, childhood adversity and late treatment. Bipolar I and bipolar II disorder carry comparable burdens of illness and suicide risk. ^[1][6]

• Systematic screening of depressed patients for hypomanic or manic history is the single most effective way to reduce diagnostic delay; tools such as the Mood Disorder Questionnaire help but cannot stand alone.
• Primary prevention is limited: heritability is high, and no intervention has been proven to prevent onset in at-risk relatives. The best secondary prevention is early identification and sustained treatment after a first episode, because response is best after the first episode and declines thereafter. ^[1][5]
• Establish psychoeducation, relapse-prevention planning and social-rhythm regularity from the outset: avoid all-night activity, get morning light, take a daily walk, avoid over-stimulation when mood is unstable. ^[5]
• Monitor physical health at least annually in primary care, with weight, BMI, diet, activity, blood pressure, glucose or HbA1c, lipids, liver function and (on lithium) renal, thyroid and calcium checks.
• For lithium users, a written medication plan, annual review and crisis protocol shared between primary and secondary care reduce risk. ^[2]

Bipolar disorder in pregnancy and the postpartum period needs specialist coordinated care; NICE refers readers to its antenatal and postnatal mental health guideline, and pregnancy is a reason for re-referral from primary to secondary care. ^[2]

• Lithium: may cause fetal and neonatal harm. Early data raised concerns about major cardiac malformations (notably Ebstein anomaly), but later studies suggest the increased risk is small, and it has been reported that the risk is not significantly increased at doses of 600 mg per day or less. Standards differ globally, including contraindication in some countries. If lithium is continued, monitor levels and adjust dose in pregnancy; decrease or stop lithium two to three days before delivery to reduce maternal and neonatal toxicity, and restart at the preconception dose postpartum once stable. Consider fetal echocardiography at 16 to 20 weeks after first-trimester exposure. Neonatal toxicity ("floppy infant") with hypotonia, respiratory distress, feeding difficulties and bradycardia can last up to 14 days. Lithium is present in breast milk and caution is needed when breastfeeding. ^[3][5]
• Valproate: contraindicated for prophylaxis of migraine in pregnancy, and should not be used in epilepsy or bipolar disorder in pregnancy, or when planning pregnancy, unless other medications have failed or are unacceptable. It causes major congenital malformations (neural tube defects, cardiac, craniofacial, limb), decreased IQ and neurodevelopmental disorders in the offspring; the malformation rate is about four times that of other anti-seizure drugs and 9% to 11% in the offspring of women taking about 1000 mg per day. It should not be given to a woman of childbearing potential unless other options have failed; effective contraception, regular counselling, folic acid before conception and in the first trimester, and valproate pregnancy registry enrolment are required. ^[7]
• Antipsychotics: many (including quetiapine and olanzapine) have more reassuring data in pregnancy than lithium or valproate and are often safer first choices when an antipsychotic is needed, but decisions must be individualised.

• Lithium is licensed for acute manic and mixed episodes and maintenance from age 7; starting dose and targets are the same as for adults, with close monitoring.
• Valproate in children is subject to the same MHRA under-55 restrictions; hepatotoxicity is highest in children under two years.
• Many antipsychotics (quetiapine, risperidone) carry paediatric licences for mania in adolescents; monitor weight, glucose and lipids carefully. ^[2][9][7]
• Earlier age of onset predicts more comorbidity, substance use and suicidality; early, sustained, family-inclusive care matters.

• Lithium targets around 0.4 to 0.6 mEq per L are commonly quoted for patients 65 and older; NICE states older people should be offered the same range of treatments and services. ^[2][3]
• Start lower, titrate more slowly, and monitor fluid, nutrition, somnolence and renal function; anticholinergic and cardiometabolic burdens are higher. ^[2][7]
• Valproate and antipsychotics in older people require particular caution because of falls, sedation, hyponatraemia and cardiovascular risk.

• A careful history plus a competent mental state examination are usually enough to make the diagnosis; no blood test confirms bipolar disorder.
• Prioritise sleep and routine stabilisation, family psychoeducation, lithium where laboratory monitoring is available, or an antipsychotic/quetiapine where it is not.
• Valproate can be effective but requires strict avoidance in pregnancy and childbearing potential.
• Monitor simple parameters: weight, pulse, blood pressure, thyroid where tests exist, and watch for toxicity.
• Plan services so that the same clinician and one nurse provide continuity.

• Bipolar and related disorders span a spectrum: bipolar I, bipolar II and cyclothymic disorder, with mixed and other specified forms.
• Mania (one week or any duration if hospitalised, with marked impairment or psychosis) and hypomania (at least four days, no marked impairment) are the defining elevated states; depressive episodes dominate lifetime morbidity. ^[6][3]
• The DIG FAST mnemonic summarises the manic symptom group; DSM-5/ICD-11 criteria are used for formal diagnosis. ^[1]
• About 2.4% of people have a bipolar spectrum disorder (about 0.6% bipolar I and 0.4% bipolar II) globally; onset is in the early twenties; risk is roughly equal in men and women. ^[4][1]
• Suicide risk is greatly increased (around 6% to 7% die by suicide); risk assessment and lithium's anti-suicidal effect matter at every contact. ^[2][6]
• First-line long-term treatment is lithium, titrated to a level (0.8 to 1.2 mEq per L in mania, 0.8 to 1.0 mEq per L in maintenance), with standard baseline and annual monitoring. ^[3][2]
• For acute mania: haloperidol, olanzapine, quetiapine or risperidone, with lithium or valproate added or used when indicated; mania adjunct lithium target 0.8 to 1.2 mEq per L. ^[2][1][3]
• For bipolar depression: psychological therapy plus quetiapine 300 mg daily, fluoxetine with olanzapine, lithium or lamotrigine according to phase; CANMAT lists quetiapine, lurasidone with lithium or divalproex, lithium, lamotrigine and lurasidone as first line. ^[2][1]
• Lamotrigine is maintenance-only at 200 mg per day (100 mg with valproate), titrated slowly. ^[8]
• Valproate for acute mania at 750 mg daily in divided doses, 50 to 125 micrograms per mL in trials; strict pregnancy and under-55 restrictions apply. ^[7][2]
• Mixed features are treated on the mania pathway; rapid cycling gets the same evidence-based interventions. ^[2]
• Pregnancy care is multidisciplinary: lithium needs careful level management around delivery, and valproate is avoided unless nothing else works. ^[3][7]
• Antidepressants can precipitate hypomania or mania and are usually withdrawn once stable.

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• Bipolar and related disorders span a spectrum: bipolar I, bipolar II and cyclothymic disorder, with mixed and other specified forms.
• Mania (one week or any duration if hospitalised, with marked impairment or psychosis) and hypomania (at least four days, no marked impairment) are the defining elevated states; depressive episodes dominate lifetime morbidity.
• The DIG FAST mnemonic summarises the manic symptom group; DSM-5/ICD-11 criteria are used for formal diagnosis.
• About 2.4% of people have a bipolar spectrum disorder (about 0.6% bipolar I and 0.4% bipolar II) globally; onset is in the early twenties; risk is roughly equal in men and women.
• Suicide risk is greatly increased (around 6% to 7% die by suicide); risk assessment and lithium's anti-suicidal effect matter at every contact.
• First-line long-term treatment is lithium, titrated to a level (0.8 to 1.2 mEq per L in mania, 0.8 to 1.0 mEq per L in maintenance), with standard baseline and annual monitoring.
• For acute mania: haloperidol, olanzapine, quetiapine or risperidone, with lithium or valproate added or used when indicated; mania adjunct lithium target 0.8 to 1.2 mEq per L.
• For bipolar depression: psychological therapy plus quetiapine 300 mg daily, fluoxetine with olanzapine, lithium or lamotrigine according to phase; CANMAT lists quetiapine, lurasidone with lithium or divalproex, lithium, lamotrigine and lurasidone as first line.
• Lamotrigine is maintenance-only at 200 mg per day (100 mg with valproate), titrated slowly.
• Valproate for acute mania at 750 mg daily in divided doses, 50 to 125 micrograms per mL in trials; strict pregnancy and under-55 restrictions apply.
• Mixed features are treated on the mania pathway; rapid cycling gets the same evidence-based interventions.
• Pregnancy care is multidisciplinary: lithium needs careful level management around delivery, and valproate is avoided unless nothing else works.
• Antidepressants can precipitate hypomania or mania and are usually withdrawn once stable.

No verified related topics are listed for this page; prerequisites and related entries are left empty for the builder to populate.

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