Bipolar Disorders: Updates on Diagnosis and Treatment Approaches

Bipolar disorders (BD) comprise recurrent episodes of elevated mood and depression. The relapse rate is more than 70% in five years. Hypomania can occur in BD I and II, while mania, which can include psychosis, appears only in BD I.

TB, which affects >1% of the world’s population, has no predilection for race, sex, ethnicity, or socioeconomic status. TB I has a higher incidence than TB II (0.6% and 0.4%, respectively). The average age of onset is 18 years in TB I and 22 years in TB II.

Three-quarters of patients have a history of co-occurring mental conditions, typically anxiety, impulse control and attention-deficit/hyperactivity disorders, and substance use disorders, which are associated with worse outcomes.

One third of TB patients will attempt suicide; 26% of cases occur within six weeks of hospital discharge. Patients with anxious distress have a higher risk of suicide, a longer duration of illness, and a worse response to medication.

TBs are multifactorial conditions with a genetic predisposition affected by stress and the environment.

Children of parents with TB have a 4% to 15% risk of being affected.

Acute stressors are usually associated with the initial onset of the disease and sometimes its recurrence, and include stressful life events, adverse childhood events and trauma, suicide of a family member, and disruptions in the sleep cycle. Biological susceptibility, central and peripheral nervous system inflammation, abnormal endocrine and neuronal pathways, and inheritance patterns of mitochondrial dysfunction have been linked to bipolar disorders.

Patients typically present with depression or anxiety or with mixed features, including co-occurring mania and depression. This depression may be indistinguishable from unipolar depression and often begins in early childhood. Women are more susceptible during hormonal fluctuations (menstruation, childbirth and menopause).

Diagnosis may be delayed because depressive episodes may occur before a mixed, manic, or hypomanic episode manifests. Depressed patients should be specifically asked about symptoms of mania or hypomania. Up to 25% of patients may have a seasonal pattern.

The US Preventive Services Task Force recommends screening for depressive disorders in patients ≥ 12 years of age, including perinatally pregnant patients, in an outpatient setting as long as it includes accurate diagnosis, psychotherapy, and follow-up.

The most used tool is the Health Questionnaire appropriate to the patient’s age. TB II is often not recognized in primary care practices unless specifically looked for. Other tools, such as the Mood Disorders Questionnaire, may be useful in excluding bipolar disorders, but are usually not sufficient to confirm the diagnosis.

General medical conditions are more common in patients with bipolar disorders compared to age-matched cohorts. Appropriate evaluation of diabetes mellitus and lipid abnormalities, which are commonly associated with TB, is needed. Evidence supports the use of metformin for the adverse metabolic effects of treatment.

Early diagnosis and treatment improves prognosis by reducing the risk of relapse and doubling the response rate to drugs. Medications are the mainstay of therapy and are selected according to the stage of presentation of the disease, the severity and the patient’s own factors.

Among patients using pharmacotherapy, relapse occurs in up to 25% in the first year; the risk increases to 40% among untreated patients and to more than 70% within five years, regardless of treatment approach. Therefore, it is recommended to continue pharmacotherapy indefinitely.

Co-management with a psychiatrist can help the physician navigate diagnostic and therapeutic challenges. Patients should be educated about the teratogenic effects of many mood stabilizers, the importance of using reliable contraception, and the possibility of risky sexual behavior during mania.

Patients with TB should be encouraged to keep a record of medications they have used in the past due to the chronic and relapsing nature of the disorder. Monotherapy with antidepressants is contraindicated in patients with mixed features, manic episodes or TB I.

> Acute mania: Mania is defined as a defined period of abnormal and persistently elevated, expansive or irritable mood and by an abnormal and persistent increase in activity or energy that lasts at least a week and is present for most of the day. day, almost every day (or any duration if hospitalization is necessary). Early signs of relapse include sleep disturbances, agitation, increased goal orientation, and disruption in the patient’s usual routine. These patients require hospitalization due to the risk of harm to themselves or others. The goals of initial treatment include adequate sleep and reduction of psychotic symptoms.

Evidence supports the use of mood stabilizers, such as lithium, valproic acid, and antipsychotics. Valproic acid is often used because it can be titrated quickly. Lithium is the treatment of choice for classic euphoric mania, defined by a predominance of manic symptoms associated with elevated mood, and is a proven anti-suicidal agent. It is often given along with an antipsychotic and a benzodiazepine (e.g., quetiapine, risperidone), which can help with sleep problems.

> Mixed characteristics: Denotes presentations with characteristics of depression and hypomania or mania at the same time. For these patients, atypical antipsychotics (aripiprazole, asenapine, olanzapine, quetiapine, risperidone) or anticonvulsants (carbamazepine) are usually used. Despite symptoms, monotherapy with antidepressants is contraindicated.

> Acute depression: Quetiapine, cariprazine, lurasidone in combination with lithium or valproic acid, and electroconvulsive therapy appear to be the fastest-acting therapeutic options. Although patients are highly sensitive to antipsychotics, these drugs are associated with weight gain, diabetes, and extrapyramidal effects. When mood stabilizers alone are insufficient, augmentation of treatment with antidepressants such as selective serotonin reuptake inhibitors or bupropion, which are less likely to induce mania, may be considered. When treating sleep disturbance in depressed patients, trazodone should be avoided because it may induce mania.

> Maintenance therapy: High-quality evidence supports the use of lithium, lamotrigine, quetiapine, quetiapine in combination with lithium or valproic acid, aripiprazole and olanzapine in patients with TB; Each has specific advantages and disadvantages. Suicide risk is reduced when patients are more satisfied with their care, when they use lithium therapy, and when alcohol and tobacco use disorders are treated.

> Augmentation Therapies: Enhancement therapies such as omega-3 fatty acids, light therapy, N-acetylcysteine, ketamine and probiotics show promise in different phases of the disease. However, they lack sufficient evidence to recommend its current use.

In the maintenance phase, examination of patients should focus on depressive, manic, and sleep symptoms; suicide risk; substance use disorders; comorbid conditions; and general medical health. Extrapyramidal effects are usually early and may include akathisia, parkinsonism, and other movement disorders, such as dystonias and dyskinesias.

Akathisia requires monitoring because it can mimic worsening mania or anxiety. Sometimes a change in regimen is required because it can lead to suicide. Tardive dyskinesia is a potentially irreversible movement disorder that can occur within months of starting antipsychotic treatment in older people, who are also at risk of stroke and other cardiovascular events, and in patients with neurological vulnerability (e.g. HIV or other diseases of the nervous system).

Dose reduction should be considered regularly in patients taking antipsychotics. Lower doses may be necessary in children or older adults, patients with chronic diseases, and those who are underweight. Higher doses are required for patients with severe psychosis.

Electroconvulsive therapy is effective for mania and psychotic depression. It is often reserved for older patients and those who have refractory disease and catatonia for which pharmacotherapy has failed. It can be used for emergencies, such as in patients with acute psychosis and suicidal behavior.

Psychosocial stress triggers mania and depression. Behavioral interventions, such as basic psychoeducation and cognitive-behavioral therapy, are adjuncts that improve social function and reduce the need for medications, number of hospitalizations, and relapse rates. Nutrition, exercise, coping strategies, and positive attitudes toward good health are also beneficial.

Although there is limited data supporting family interventions in patients with TB, those who have social support in recognizing early warning signs of recurrence appear to have lower risk of recurrence and hospitalization and better functioning. Patients who receive intensive psychotherapy or group therapy have fewer relapses and longer periods of well-being.

Patients with frequent episodes of mania may benefit from strategies that emphasize medication adherence, while those with more depressive symptoms benefit from treatments focused on coping strategies and cognitive behavioral therapy. Patients, families, and caregivers should establish a plan to immediately address suicidal and homicidal ideation if they become evident.