Bipolar Episodes With Mixed Features

Medically Reviewed by Smitha Bhandari, MD on August 25, 2022
Written by Matthew Hoffman, MD
5 min read

Mixed features refers to the presence of high and low symptoms occurring at the same time, or as part of a single episode, in people experiencing an episode of mania or depression. In most forms of bipolar disorder, moods alternate between elevated and depressed over time. A person with mixed features experiences symptoms of both mood "poles" -- mania and depression -- simultaneously or in rapid sequence. 

Virtually anyone can develop bipolar disorder. About 2.5% of the U.S. population -- nearly 6 million people -- has some form of bipolar disorder.

Mixed episodes are common in people with bipolar disorder -- half or more of people with bipolar disorder have at least some mania symptoms during a full episode of depression. Those who develop bipolar disorder at a younger age, particularly in adolescence, may be more likely to have mixed episodes. People who develop episodes with mixed features  may also develop "pure" depressed or "pure" manic or hypomanic phases of bipolar illness.  People who have episodes of major depression but not full episodes of mania or hypomania also can sometimes have low-grade mania symptoms. These are symptoms that are not severe or extensive enough to be classified as bipolar disorder. This is referred to as an episode of "mixed depression" or a unipolar (major) depressive episode with mixed features.

Most people are in their teens or early 20s when symptoms from bipolar disorder first start. It is rare for bipolar disorder to develop for the first time after age 50. People who have an immediate family member with bipolar are at higher risk.

Mixed episodes are defined by symptoms of mania and depression that occur at the same time or in rapid sequence without recovery in between..

  • Mania with mixed features usually involves irritability, high energy, racing thoughts and speech, and overactivity or agitation.
  • Depression during episodes with  mixed features  involves the same symptoms as in  "regular" depression, with feelings of sadness, loss of interest in activities, low energy, feelings of guilt and worthlessness, and thoughts of suicide.

This may seem impossible. How can someone be manic and depressed at the same time? The high energy of mania with the despair of depression are not mutually exclusive symptoms, and their co-occurrence may be much more common than people realize. 

For example, a person in an episode with mixed features could be crying uncontrollably while announcing they have never felt better in their life. Or they could be exuberantly happy, only to suddenly collapse in misery. A short while later they might suddenly return to an ecstatic state.

Mood episodes with mixed features can last from days to weeks or sometimes months if untreated. They  may recur ,and recovery can be slower than during episodes of "pure" bipolar depression or "pure" mania or hypomania.

The most serious risk of mixed features during a manic or depressive episode is suicide. People with bipolar disorder are 10 to 20 times more likely to commit suicide than people without bipolar disorder. Tragically, as many as 10% to 15% of people with bipolar disorder eventually lose their lives to suicide.

Evidence shows that during episodes with mixed features, people may be at even higher risk for suicide than people in episodes of bipolar depression.

Treatment reduces the likelihood of serious depression and suicide. Lithium (Eskalith, Lithobid) in particular, taken long term, may help to reduce the risk of suicide.

People with bipolar disorder are also at higher risk for substance abuse. Nearly 60% of people with bipolar disorder abuse drugs or alcohol. Substance abuse is associated with more severe or poorly controlled bipolar disorder.

Manic or depressive episodes with mixed features generally require treatment with medication. Unfortunately, such episodes are more difficult to control than an episode of pure mania or depression. The main drugs used to treat episodes with mixed features are mood stabilizers and antipsychotics.

Mood Stabilizers

While lithium is often considered a gold standard treatment for mania, it may be less effective when mania and depression occur simultaneously, as in a manic episode with mixed features. Lithium has been used for more than 60 years to treat bipolar disorder. It can take weeks to work fully, making it better for maintenance treatment than for acute manic episodes. Blood levels of lithium and other lab test results must be monitored to avoid side effects.

Valproic acid (Depakote) is an antiseizure medication that also levels out moods in bipolar disorder. It has a more rapid onset of action, and in some studies has been shown to be more effective than lithium for the treatment of manic episodes with mixed features.

Some other antiseizure drugs, such as and carbamazepine (Tegretol) and lamotrigine (Lamictal), are also effective mood stabilizers.

Antipsychotics

Many atypical antipsychotic drugs are effective FDA-approved treatments for manic episodes with mixed features. These includearipiprazole (Abilify), asenapine (Saphris), cariprazine (Vraylar), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon). Antipsychotic drugs are also sometimes used alone or in combination with mood stabilizers for preventive treatment.

Electroconvulsive Therapy (ECT)

Despite its frightening reputation, electroconvulsive therapy (ECT) is an effective treatment for any phase of bipolar disorder, including manic episodes with mixed features. ECT can be helpful if medication fails or can't be used.

Treatment for Depression in Mixed Bipolar Disorder

Common antidepressants such as fluoxetine (Prozac, Sarafem), paroxetine (Paxil), and sertraline (Zoloft) have been shown to worsen mania symptoms without necessarily improving depressive symptoms when depressive and manic symptoms occur together. Most experts therefore advise against using antidepressants during episodes with mixed features. Mood stabilizers (particularly Depakote), as well as atypical antipsychotic drugs, are considered the first-line treatments for mood episodes with mixed features.

Bipolar disorder usually  involves recurrences of mixed, manic, or depressed phases of illness. Therefore, it is usually recommended that medications be continued in an ongoing fashion after an acute episode resolves in order to prevent relapses. This is sometimes called maintenance treatment.