Before we discuss bipolar disorders, let’s review the terms “Mood” and “Affect”

AFFECT: A person’s immediate expression of emotion

MOOD: The more sustained emotional makeup of a person’s personality 

What are Mood Disorders?

Mood disorders are group of psychiatric disorders in which disturbances of mood or affect are severe and persistent enough to cause significant problems in an individual’s life. Moods themselves are not pathological and many of us have experienced a range of mood states. But when moods become severe and persistent enough to cause dysfunction and issues in an individual’s life, then we use the term “mood disorder.”

Symptoms of mood disorders usually occur in discrete periods we call episodes. Episodes can last for days, weeks, months, or even years. During these “episodes,” there is a significant change in an individual’s mood which may negatively impact work performance, relationships, or other important areas of functioning. The most common mood disorder is Major depressive disorder (MDD), often referred to as “Unipolar depression.”

Bipolar disorders are also mood disorders that differ from unipolar depression by the presence of elevated mood states called hypomania or mania.

Bipolar Disorders

Bipolar disorder is a mental disorder that causes dramatic shifts in a person’s mood, energy, and ability to think clearly. Individuals with bipolar disorder experience high moods, known as mania or hypomania, and low moods, known as depression. These moods differ from the typical ups-and-downs most individuals’ experience. Individuals with bipolar disorder can also experience mixed episodes, which include a combination of depressive and manic/hypomanic symptoms.

Mood disorders, as we currently understand them, occur on a spectrum. As of the writing of this post, mood disorders are categorized separately in the DSM 5-TR as “depressive disorders” and “bipolar and related disorders.” Major depressive disorder (MDD), also call unipolar depression, is one type of depressive disorder characterized by one or more major depressive episodes. Major depressive disorder, by definition, is not associated with hypomanic or manic episodes. As such, MDD it is differentiated diagnostically and categorically from bipolar disorder.

What is Mania and Hypomania?

Mania is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood with abnormally and persistently increased goal-directed activity or energy that lasts at least 1 week. Hypomania is similar to mania but less severe. A hypomanic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy that lasts at least four consecutive days. Hypomanic episodes are typically not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic. During a manic or hypomanic episode, a combination of the following symptoms is present and represents a noticeable change in behavior (see below).

If drugs or medications cause the above symptoms, then we consider this a medication (or substance)-induced manic or hypomanic state. However, a full manic or hypomanic episode that emerges due to medication (e.g., antidepressants) or drugs (e.g., cocaine, amphetamines) but persists beyond the physiological effect of the medication or drug is sufficient for a bipolar diagnosis.

Bipolar Subtypes

Bipolar and related disorders include bipolar I disorder, bipolar II disorder, cyclothymic disorder, substance/medication-induced bipolar and related disorder, bipolar and related disorder due to another medical condition, and other/unspecified bipolar and related disorder. 

Mean age at onset of the first manic, hypomanic, or major depressive episode is approximately 18 years for bipolar I disorder and mid-20s for bipolar II disorder. Bipolar disorder most often begins with a depressive episode and is not recognized as bipolar disorder until a hypomanic or manic episode occurs; this happens in about 12% of individuals with the initial diagnosis of major depressive disorder. Many individuals experience several episodes of major depression prior to the first recognized hypomanic or manic episode. Individuals with major depressive disorder, who later are diagnosed with a bipolar disorder, often have an onset of the illness in adolescence, a history of psychotic features, or a family history of bipolar illness.

Because depressed episodes often precede the first hypomanic or manic episode, most patients with bipolar disorder are initially misdiagnosed as having major depressive disorder. This is a major reason why those with bipolar disorder go undiagnosed or misdiagnosed for many years (about 10 years).

It is also worth mentioning that classic SSRI/SNRI antidepressants such as sertraline (Zoloft), Paroxetine (Paxil), Citalopram (Celexa), Fluoxetine (Prozac), Venlafaxine (Effexor), and Duloxetine (Cymbalta) are often ineffective or may induce irritability, agitation, hypomania, and/or rapid cycling of moods in individuals with bipolar disorder.

Unfortunately, bipolar depression and unipolar depression are very difficult, if impossible, to differentiate. Clinical experience and some empirical evidence suggest that hypersomnia (more sleeping), apathy, increased appetite (craving for simple carbohydrates), and weight gain may be more suggestive of bipolar depression, but this is controversial.

It is also important to mention that individuals with bipolar disorder experience depressive symptoms more often than hypomanic, manic, or mixed episodes. That is, most mood episodes experienced by someone with bipolar disorder are depressive.

Rapid Cycling

Rapid cycling in bipolar disorder (BD) is a descriptor that defines a subset of patients that have a large number of episodes over short periods of time. Specifically, rapid cycling is defined as having 4 or more episodes in a 12 month period, but many patients may have significantly more episodes. Individuals with rapid cycling generally have a younger age of onset, greater disease burden, and greater exposure to antidepressants. Cannabis, alcohol, caffeine, steroids, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and Tricyclic Antidepressants have been associated with inducing rapid cycling. 

The Neurobiology of Bipolar Disorder

Bipolar disorder is a complex disorder. The cause of bipolar disorder is not fully understood but there are several contributing factors that include genetic influences (e.g., family history of bipolar illness), environmental influences (e.g., stress and circadian rhythm disruptions), and biochemical factors (e.g., drug abuse and hormonal imbalances). Neurophysiological changes in specific neural networks in the brain have been suggested as the primary pathophysiology of bipolar disorder.

Disrupted circadian rhythms are often harbingers of mood episodes in individuals with underlying bipolar disorder. It is unclear whether the natural course of the illness causes disturbances in sleep or disturbances in sleep precipitate mood episodes. However, it is well known that disruptions in an individual’s sleep cycle present a major risk for mood instability. This is particularly true for those with mood disorders such as bipolar disorder and major depressive disorder.

Human studies have found increased concentrations of noradrenaline (norepinephrine) and dopamine (DA) and decreased concentrations of serotonin (5-HT) in manic patients. This suggests that norepinephrine and dopamine dysregulation may play a primary role in manic symptoms. In addition to monoamine dysregulation, there is evidence implicating the glutamate and GABA systems in the pathophysiology of bipolar disorder. Animal studies suggest increased glutamatergic neurotransmission via NMDA receptors in manic patients. In addition, the efficacy of anticonvulsants, NMDA antagonists (e.g., ketamine), and benzodiazepines in the treatment of bipolar disorder suggests that glutamate and GABA systems are involved.

Circadian rhythms are consistently disturbed in patients with bipolar disorder. Researchers are investigating whether circadian rhythm disturbances might lead to mania given the fact that lithium deactivates the transcription factor GSK3B enzyme which is thought to reset the circadian clocks and restore normal brain functioning.

Functional Neuroimaging Studies have demonstrated or suggested that the following areas are implicated in bipolar disorder: prefrontal cortex, limbic areas such as the hippocampus, amygdala, anterior cingulate, and the ventral striatum (nucleus accumbens). A number of brain circuits have been implicated in the pathophysiology of bipolar disorder. Many of these circuits are involved in the regulation of emotion and cognition. Decreased activation of the orbitofrontal (OFC) circuits during a go-no go test in manic patients may explain the impulsive behaviors. Recall that the OFC is an important region within the prefrontal cortex involved in impulse-control and compulsive behaviors. The dorsolateral prefrontal cortex is involved in attentional processes and its dysfunction may also play a role in the pathophysiology of bipolar disorder. Decreased size and activity of the prefrontal cortex (PFC) has been demonstrated in patients with bipolar disorder—similar to that found in patients with unipolar depression. Interestingly, after four weeks of lithium treatment (but no valproic acid) there was an increase in gray matter volume in bipolar patients. Amygdalae are larger and more active in the bipolar patients. Bipolar disorder may be the result of abnormal interactions between the PFC and subcortical regions such as the amygdala—an abnormality not usually seen with unipolar depression. Reasons for the reduction in brain volumes and cell loss remain a mystery but could be from environmental stressors, neurodevelopmental abnormalities, and/or dysfunction in neurotransmitter systems.

Treatment of Bipolar Disorder

If left untreated, bipolar disorder usually worsens. And this highlights the importance of a good treatment plan that includes psychotherapy, mood-stabilizing medications, a healthy lifestyle, maintenance of sobriety, a consistent sleep schedule and early identification of symptoms. The management of bipolar disorder is multidimensional. The main objectives of pharmacotherapy (medication management) in bipolar disorder are to treat the acute manic/hypomanic and depressive episodes and minimize their recurrence.

Manic episodes are treated with one or more of the following: Lithium, valproate (Depakote), carbamazepine (Tegretol), lamotrigine (Lamictal), asenapine (Saphris), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), ziprasidone (Geodon), cariprazine (Vraylar), or aripiprazole (Abilify), clonazepam (Klonopin), diazepam (Valium), or lorazepam (Ativan).

Bipolar depressive episodes are treated with one or more of the following: Lithium, cariprazine (Vraylar), quetiapine (Seroquel), lurasidone (Latuda), Fluoxetine-Olanzapine combination (OFC), or lamotrigine (Lamictal).

For more information about medication options for bipolar disorder, visit Medication Algorithms for Mental Disorders.

Comorbid symptoms such as inattention, low energy, and low motivation can be safely treated with classic psychostimulants as long as a mood stabilizer is also prescribed. Severe anxiety, including social anxiety, can be safely managed with the addition of clonidine, propranolol, gabapentin, pregabalin, or benzodiazepines. In general, antidepressants should be avoided.

Neuromodulatory modalities such as neurofeedback, Transcranial Magnetic Stimulation (TMS), and ketamine infusion therapy should be considered if medication and therapy are not effective (or only partially effective).

While medication, neuromodulatory modalities, and drug abstinence are important in the management of bipolar disorder, they are considered components of a comprehensive treatment plan. As such, individual and/or family psychotherapy and psychoeducation should be incorporated.

Bipolar Depression

Bipolar Mania and Mixed States

Bipolar Maintenance

Observational studies suggest that with each episode of illness the time between episodes shortens. This highlights the importance of relapse prevention, which may improve long-term prognosis. For Mania Prevention: Lithium (Reduces suicide rates and overall mortality), Aripiprazole, Quetiapine, Olanzapine, Valproic Acid.  For Depression Prevention: Quetiapine, Lamotrigine, Lithium (Reduces suicide rates and overall mortality), Lurasidone

Final Comments

It is important to remember that the management of neuropsychiatric disorders is multifactorial, and medication is only one component. As stated previously, integrating treatment modalities such as psychotherapy, mentorship, sobriety, mindfulness-based stress reduction, and the pursuit of passionate hobbies/interests are all very important in the management of bipolar disorder.

BIPOLAR DISORDER DIAGNOSIS AND TREATMENT GUIDELINES (PDF)

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Helping Someone with Bipolar Disorder – HelpGuide.org

How to support someone during a difficult time