The emphasis of the treatment of bipolar disorder is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms. Treatment methods include pharmacological and psychological techniques.

Bipolar disorder is a serious and debilitating mental health disorder, which causes patients to experience extreme highs and lows, such as mania and major depression.

Principles The use of psychotherapy to treat bipolar disorder has been found to reduce the relative risk of relapse at post-treatment (risk ratio=0.66) and follow-up time points (risk ratio=0.74).

Although treatment for bipolar disorder was once centered around medications called mood stabilizers, which are used to prevent or control episodes of mania or depression, the United Nations Special Rapporteur in the right to health has said,

Although the lifetime rate of suicide attempt in bipolar disorder is high (34%), guidelines for assessment of suicide risk are supported by evidence of "low" "overall strength". Although hospitalization was once a recommended practice, the United Nations' Committee on Rights of Persons with Disabilities recommends abolishing institutionalization and involuntary treatments "such as sedatives, mood stabilizers, electro-convulsive treatment, and conversion therapy".

+Mood stabilisers Treatment NNT for depressive relapse NNT for manic relapse Efficacy in Acute Mania Efficacy in Acute Depression Common Side Effects Serious Side Effects Safety during pregnancy Routes of Administration Aripiprazole monotherapy 50 6.2 ++ - Weight gain, nausea, vomiting, constipation, akathisia, dizziness, extrapyramidal symptoms, headache, insomnia, sedation, tremor, blurred vision, anxiety, restlessness, fatigue Seizure (0.1-0.3%), suicidal behaviour, blood clots (<1%), agranulocytosis, leukopenia (<1%), neutropenia(<1%), pancreatitis (<0.1%), metabolic syndrome, neuroleptic malignant syndrome, tardive dyskinesia, angioedema (<1%), rhabdomyolysis Pregnancy Category: B3 (Au) C (US) Oral, Intramuscular Aripiprazole adjunct to lithium/valproate 33.3 10 ++ - As above As above As above As above Lamotrigine monotherapy 20.2 50.4 - ++/+ Rash, abdominal pain, indigestion, diarrhoea, nausea, vomiting, asthenia, ataxia, coordination problem, dizziness, headache, insomnia, sedation, tremor, vertigo, blurred vision, diplopia, anxiety, depression, dysmenorrhoea, rhinitis, pain Erythema multiforme (<0.1%), Stevens–Johnson syndrome (0.08-0.8%), toxic epidermal necrolysis (0.08-0.8%), anaemia (<0.1%), Disseminated intravascular coagulation, Eosinophilia(<0.1%), Thrombocytopenia (<0.1%), Liver failure, Drug hypersensitivity syndrome, aseptic meningitis Pregnancy Category: D (Au) C (US) Appears to have a lower propensity than carbamazepine, lithium and valproate for causing birth defects but can still cause birth defects Mucous membranes, oral Lithium monotherapy 6.1 4.4 ++ ++/+ Acne, hypothyroidism, weight gain, gastritis, xerostomia, nausea, leukocytosis, fine tremor, Hyperreflexia, Deep tendon, Nephrotoxicity, Polyuria, Potential sign of toxicity, Increased thirst, Potential sign of toxicity Bradyarrhythmia (Severe), Brugada syndrome, Sinus node dysfunction, Transient reduction in peripheral circulation as a whole, Erythema multiforme, Ataxia, Potential sign of toxicity, Coma, Pseudotumor cerebri, Increased intracranial pressure and papilledema, Seizure, Blurred vision, Potential sign of toxicity, Tinnitus, Potential sign of toxicity, Giddiness, Potential sign of toxicity, Renal interstitial fibrosis, Angioedema Pregnancy Category: D (Au) D (US) Risk of Ebstein's anomaly and other congenital heart defects. Oral Olanzapine monotherapy 17.2 4.4 +++ ++/+ Orthostatic hypotension, Peripheral edema (3% to 6%), Hypercholesterolemia (up to 24%), Hyperglycemia (0.1% to 17.4%), Increased appetite (3% to 24%), Increased prolactin level (31.2% to 61.1%), Serum triglycerides raised (up to 40%), Weight gain, Constipation, Xerostomia, Akathisia, Asthenia, Dizziness, Sedation, Tremor, Personality disorder (8%), Accidental injury (4% to 12%) Sudden cardiac death, Diabetic coma with ketoacidosis, Diabetic ketoacidosis, Hyperglycemic hyperosmolar state, Acute hemorrhagic pancreatitis, Venous thromboembolism, Immune hypersensitivity reaction, Cerebrovascular disease, Seizure (0.9% ), Status epilepticus, Suicidal intent (0.1% to 1% ), Pulmonary embolism Pregnancy Category:

C (Au) C (US) Oral, intramuscular Olanzapine adjunct to lithium/valproate 6.2 11.2 +++ - As above As above As above As above Quetiapine monotherapy 3.3 2.4 ++ +++ Orthostatic Hypertension, Tachycardia (0.5% to 7%), Serum cholesterol raised (7% to 18%), Serum triglycerides raised (8% to 22%), Weight gain (3% to 23%), Abdominal pain, Constipation, Increased appetite, Indigestion, Vomiting, Xerostomia, Increased liver enzymes, Backache, Asthenia, Dizziness, Extrapyramidal signs, Headache, Insomnia, Lethargy, Sedation, Tremor, Agitation (6% to 20%), Nasal congestion, Pharyngitis (4% to 6%), Fatigue, Pain Syncope (0.3% to 1%), Diabetic ketoacidosis, Pancreatitis, Agranulocytosis, Leukopenia, Neutropenia (0.3%), Anaphylaxis, Seizure (0.05% to 0.5%), Tardive dyskinesia (0.1% to less than 5%), Suicidal thoughts, Priapism, Neuroleptic malignant syndrome (rare ) Pregnancy Category:

B3 (Au) C (US) Oral Quetiapine plus lithium/valproate 5.9 7.1 +++/++ +++ As above As above As above As above Risperidone 4 36.4 +++ - Rash, hyperprolactinaemia, weight gain, constipation, diarrhoea, excessive salivation, increased appetite, indigestion, nausea, vomiting, upper abdominal pain, dry mouth, extrapyramidal side effects, dizziness, sedation, akathisia, blurred vision, anxiety, cough, nasal congestion, nasopharyngitis, pain in throat, upper respiratory tract infection, fatigue and generalised pains Prolonged QT interval, sudden cardiac death, syncope, diabetic ketoacidosis, hypothermia, pancreatitis, Agranulocytosis, Leukopenia, Neutropenia, Thrombocytopenia, Thrombotic thrombocytopenic purpura, stroke, seizure, tardive dyskinesia, priapism, pulmonary embolism, neuroleptic malignant syndrome Pregnancy Category:

B3 (Au) C (US) Oral, Intramuscular Risperidone plus treatment as usual 15.8 7.9 +++ - As above As above As above As Above Valproate monotherapy 10.5 21.3 ++/+ - Abdominal pain, diarrhoea, indigestion, loss of appetite, nausea, vomiting, asthenia, dizziness, feeling nervous, headache, insomnia, sedation, tremor, Amblyopia, Blurred vision, Diplopia, infectious disease, influenza Palpitation, tachycardia, hyperammonaemia, pancreatitis, thrombocytopaenia, liver failure, immune hypersensitivity reaction, hyperammonaemic encephalopathy, deafness Pregnancy Category:

D (Au) D (US)

Has the highest propensity of all anticonvulsants for causing birth defects. Around 6-11% of children born to mothers that used the drug during pregnancy are born with birth defects. Oral Ziprasidone and treatment as usual 55.1 14.1 ++/+ - Rash, weight gain, constipation, diarrhoea, indigestion, nausea, vomiting, xerostomia, akathisia, anxiety, asthenia, extrapyramidal side effects, dizziness, headache, sedation, abnormal vision, respiratory tract infection Prolonged QT interval, syncope, torsades de pointes, diabetes mellitus, hyperglycaemia, hyperprolactinaemia, dysphagia, bone marrow depression, neuroleptic malignant syndrome, seizure, tardive dyskinesia, priapism Pregnancy Category:

B3 (Au) C (US) Oral, intramuscular Legend:

- negligible/very low/clinically insignificant effect

+ weak effect

++ moderate-level effect

+++ strong effect

Regulatory status of mood stabilisers

Drug FDA approved for acute mania/mixed episodes? FDA approved for bipolar depression? FDA approved for bipolar maintenance? TGA approved for acute mania/mixed episodes? TGA approved for bipolar depression? TGA approved for bipolar maintenance? MHRA approved for acute mania/mixed episodes? MHRA approved for bipolar depression MHRA approved for bipolar maintenance Aripiprazole Yes No Yes (as an adjunct, yes) No No Yes Yes No Yes (for mania prevention) Asenapine Yes No No Yes No Yes Yes No No Carbamazepine Yes No No No No Yes No No Yes Cariprazine Yes Yes No Haloperidol No No No Yes No No No No No Lamotrigine No No Yes No No Yes No No Yes (depressive episodes) Lithium Yes No Yes Yes No Yes Yes No Yes Olanzapine Yes No (yes when in conjunction with fluoxetine) Yes Yes No Yes (as an adjunct to valproate/lithium) Yes No No Quetiapine Yes Yes Yes Yes Yes Yes Yes Yes Yes Lurasidone Yes Risperidone Yes No Yes Yes No Yes Yes No No Valproate Yes No No No No Yes Yes No Yes Ziprasidone Yes No No (yes as adjunct) Yes No No No No No Zuclopenthixol No No No Yes No No No No No

Mood stabilizers

Lithium salts

Lithium salts have been used for centuries as a first-line treatment for bipolar disorder. In ancient times, doctors would send their mentally ill patients to drink from "alkali springs" as a treatment. Although they were not aware of it, they were actually prescribing lithium, which was present in high concentration within the waters. The therapeutic effect of lithium salts appears to be entirely due to the lithium ion, Li+.

Its exact mechanism of action is uncertain, although there are several possibilities such as inhibition of inositol monophosphatase, modulation of G proteins or regulation of gene expression for growth factors and neuronal plasticity. There is strong evidence for its effectiveness in acute treatment and prevention of recurrence of mania. It can also be effective in bipolar depression, although the evidence is not as strong. It is also effective in reducing the risk of suicide in patients with mood disorders.

Potential side effects from lithium include gastrointestinal upset, tremor, sedation, excessive thirst, frequent urination, cognitive problems, impaired motor coordination, hair loss, and acne. Excessive levels of lithium can be harmful to the kidneys, and increase the risk of side effects in general. As a result, kidney function and blood levels of lithium are monitored in patients being treated with lithium.

For maintenance treatment of bipolar disorder with lithium, a recent review concludes that the standard lithium serum level should be 0.6–0.8 mmol/L, with optional reduction to 0.4-0.6 mmol/L in case of good response but poor tolerance or an increase to 0.8-1.0 mmol/L in case of insufficient response and good tolerance. For the elderly, slightly lower lithium levels of 0.4-0.6 mmol/L are recommended, with the option to go up to 0.7 or 0.8 mmol/L at ages 65‐79, and up to a maximum of 0.7 mmol/L over age 80.

Lithium levels of 0.8-1.0 are effective for acute mania. For a faster onset of action, it is recommended to use an antipsychotic with evidence for treating mania.

Monitoring is generally more frequent when lithium is being initiated, and the frequency can be decreased once a patient is stabilized on a given dose. Thyroid hormones should also be monitored periodically, as lithium can increase the risk of hypothyroidism. There is a high baseline risk of hypothyroidism among BD patients regardless of the treatment used, so monitoring should also be extended to those on other medication. Those on lithium or quetiapine do show a statistically significant elevated risk over others.

Lithium has also been proven in clinical trials to prevent suicide in people with bipolar disorder. In addition to its effects on suicide, lithium also decreases all-cause mortality in people with bipolar disorder.

Anticonvulsants