How Exactly Do Antidepressants Work?


Did you know that over 25 million people worldwide take antidepressants? But even with this high usage, many researchers aren’t sure exactly how antidepressants like selective serotonin reuptake inhibitors (SSRIs) work. Despite this treatment being around since the 1950s, there are still many unknowns, such as why they take time to become effective or why only 66% of patients respond to treatment. However, a recent study published in Molecular Psychiatry shares new findings on the molecular reasons behind treatment success.

Mood Disorders

Mood disorders consist of emotionally inconsistent psychological states, or emotional struggles causing loss of function in daily life. These disorders include major depressive disorder, bipolar disorder, PMDD, disruptive mood dysregulation disorder, and seasonal affective disorder (SAD). In many cases, doctors prescribe antidepressants to patients with mood disorders.

Symptoms vary based on disorder, but may include:

  • Persistent sadness
  • Severe irritability
  • Anxiety and outbursts
  • Fatigue
  • Mania
  • Behavioral changes
  • Impaired ability to function
  • Suicidal ideations
  • Difficulty with drinking and drugs

Learn more about mood disorders here.

New Findings on Antidepressants

What causes depression? If you said “my brain,” you’re correct. In many cases, depression is caused by low levels of neurotransmitters, or chemical messengers that transmit messages to other cells. According to ScienceDirect, four of the seven main neurotransmitters are epinephrine, norepinephrine, dopamine, and serotonin. Now, one main treatment for depression and other mood disorders are selective serotonin reuptake inhibitors (SSRIs), which increase the amount of serotonin in the brain. In fact, some researchers believe that SSRIs even contribute to brain plasticity, or the brain’s ability to heal itself.

But what researchers are not clear on is how antidepressants work on a molecular level. So, in this recent study, they traced molecular events and gene expression alterations using Prozac. First, researchers treated mice models of anxiety with Prozac for around 28 days. During this time, they saw that Prozac reduced anxiety and depression.

Next, researchers monitored mice behavior and gene expressions. Within 9 days, c-Fos gene expression significantly increased. Similarly, for human patients taking antidepressants, suicide rate falls in around 9 days. Within two weeks, the mice were moving and eating more, as well as showing less signs of stress. Similarly, antidepressants in humans take around 2-3 weeks to work.

Because of their findings, researchers then focused on the gene c-Fos. The gene creates AP-1, a transcription factor that activates genes by binding to DNA. As a result, researchers decided to study how AP-1 is produced, what genes it affects, and how this contributes to treating mood disorders.

Understanding AP-1

Once researchers discovered c-Fos and AP-1, they began studying a brain region called the cortex. This region plays a role in antidepressant responses. They discovered that antidepressants increase serotonin levels in the brain. As a result, molecular events stimulate brain cells to produce more AP-1. Generally, this occurs by day 9, which is why treatments are usually seen as effective by this point. Next, AP-1 activates genes that encourage plasticity. Thus, within 2-3 weeks, the brain begins reversing damage from depression and other mood disorders.

To verify this pathway, researchers provided mice with another substance: one that blocks AP-1 production. Even when treated with Prozac, the mice were unable to improve anxiety and depression because of the AP-1 blocker.  Moving forward, researchers hope to analyze AP-1 related genes as potential biomarkers to determine treatment efficacy. Additionally, understanding plasticity and antidepressants can assist researchers with developing new neurological treatments.

Read the source article here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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