Mood stabilizers
Lithium and the anticonvulsants carbamazepine, lamotrigine, and valproic acid are classed as mood stabilizers due to their effect on the mood states in bipolar disorder. Lithium has the best overall evidence and is considered an effective treatment for acute manic episodes, preventing relapses, and bipolar depression. Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder. Lithium is preferred for long-term mood stabilization. Lithium treatment is also associated with adverse effects and it has been shown to erode kidney and thyroid function over extended periods. Valproate has become a commonly prescribed treatment and effectively treats manic episodes. Carbamazepine is less effective in preventing relapse than lithium or valproate. Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. Valproate and carbamazepine are teratogenic and should be avoided as a treatment in women of childbearing age, but discontinuation of these medications during pregnancy is associated with a high risk of relapse. The effectiveness of topiramate is unknown. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or more symptoms similar to that of schizoaffective disorder. Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.
Consistent with this, elevated levels of Gαi, Gαs, and Gαq/11 have been reported in brain and blood samples, along with increased protein kinase A (PKA) expression and sensitivity; typically, PKA activates as part of the intracellular signalling cascade downstream from the detachment of Gαs subunit from the G protein complex. Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2 adrenergic receptors as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found. One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder. Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania. Diagnosis
Bipolar disorder is commonly diagnosed during adolescence or early adulthood, but onset can occur throughout life. Its diagnosis is based on the self-reported experiences of the individual, abnormal behavior reported by family members, friends or co-workers, observable signs of illness as assessed by a clinician, and ideally a medical work-up to rule out other causes.