Effects of Serotonin on Bipolar Disorder

Bipolar disorder is a mental illness characterized by extreme mood and behavior changes. Many people with bipolar disorder cycle through extreme highs, called mania, and lows, called depression, and sometimes manic and depressive symptoms occur simultaneously. Each individual responds differently to medications, so treatment can be frustrating and complicated.

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Because a shortage of serotonin may contribute to bipolar disorder, antidepressant drugs such as selective serotonin reuptake inhibitors, which increase serotonin activity in the brain, are prescribed in conjunction with lithium, a mood-stabilizing drug often effective in treating mania.

Brain Chemistry

The Lundbeck Institute's Brain Explorer website explains that studies of serotonin receptors show "substantial evidence for the role of serotonin in patients with bipolar disorder." Research about serotonin and the way it is metabolized indicates a reduced concentration of serotonin metabolites in bipolar disorder patients.

The neurotransmitter serotonin is involved in causing mood disorders, but theories suggesting an excess of neurotransmitters occur during a manic episode and fewer occur during depression are too simplistic. The Brain Explorer discusses research on "The Nature of Bipolar Disorder," conducted by Drs. Husseini K. Manji and Robert H. Lenox, psychiatrists at Wayne State University School of Medicine, that suggests "it is the effectiveness of the cell functioning under the modification and control of neurotransmitters that underlies the pathoetiology of mood disorders."


Serotonin plays an important part in mood regulation, and medications affecting serotonin in the brain are used to treat people suffering from depressive illness and depressive phases of bipolar disorder. However, Drs. Pedro L. Delgado and Francisco A. Moreno, of the Department of Psychiatry, University of Arizona Medical Center, assert that while serotonin is involved in depression, "the specific impairment that underlies depression is unclear and is likely to vary among patients."

In her Bipolar Beat column, psychiatrist and author Candida Fink, M.D., writes about fluoxetine as a bipolar disorder medication and warns, "although mania grabs all the headlines, the recurrent and severe depressive episodes experienced by people with bipolar disorder are typically the most devastating and dangerous of the cycles." SSRI antidepressants are often the first medications given to bipolar patients, but without an accompanying mood stabilizer, mania could be induced, worsening the illness.


Serotonin-regulating medications may not be appropriate treatment for bipolar disorder, because they may cause manic episodes and rapid cycling between depression and mania. When SSRIs are used for bipolar disorder, they should be prescribed in conjunction with a mood stabilizer to prevent the switch to mania.

People in the manic phase of bipolar disorder experience abnormally elevated moods lasting a week or more, with symptoms such as inflated self-esteem, decreased need for sleep, excessive talkativeness and activity, racing thoughts, distractibility, psychomotor agitation, and involvement in pleasurable but risky behaviors, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

Serotonin Syndrome

Combining certain medications increases serotonin levels and may trigger serotonin syndrome, a rare but serious condition. Serotonin syndrome is caused by using "serotonergic" drugs, such as SSRIs, along with other substances that elevate the brain’s serotonin levels, including amphetamines, L-tryptophan, ecstasy and LSD, and migraine medications containing triptans.