It can be challenging to find an antidepressant that works for you. Learn more about your treatment options for depression, including esketamine for faster relief.

Antidepressants are one of the most commonly prescribed medications in the United States, as more than 1 in 5American adults will experience depression in their lifetimes. Antidepressants can start working within one to two weeks, but for many individuals, relief may not come soon enough. With no end to their suffering in sight, far too many people resort to taking their own lives.

Suicide remains one of the leading causes of death in the nation. Among American teens and young adults, suicide rates are now among the highest on record. Such startling statistics beg the questions: Why does it take so long for antidepressants to work? And what treatment options are available for faster relief?

Feelings of depression or anxiety can lead to suicidal thinking. If you or a loved one is experiencing suicidal thoughts or tendencies, call the National Suicide Prevention Hotline at 1-800-273-8255.

Time Until Initial Improvement

Initial improvement of depressive symptoms can occur in one to two weeks of starting an antidepressant. However, many people who take antidepressants do not notice a significant improvement in their symptoms with the first drug they try. Moreover, many individuals who do not improve with their first trial of antidepressants fail to respond to subsequent trials. These statistics are concerning because the poor response to antidepressants is predictive of higher rates of chronic depression and poorer overall health.

Timeline for Full Benefits

Generally, most people achieve maximum relief of depressive symptoms within two to three months of antidepressant use. If an individual does not show improvement within four to six weeks of starting an antidepressant, further steps are usually taken. Such steps may include increasing drug dosage, or switching to or adding another antidepressant. Additional steps may include adding other kinds of psychiatric medications, psychotherapy or somatic treatments to care.

Variables in Antidepressant Response Time

Some individuals respond more quickly to antidepressants than others, leaving many people wondering, “Why does it take so long for antidepressants to work?” Still, many people do not respond to antidepressants at all. What determines who will and who won’t respond to an antidepressant? To understand the answers to these questions, some basic understanding of how antidepressants work is needed.

The most commonly prescribed antidepressants are known as SSRIs, or selective serotonin reuptake inhibitors. SSRIs work by elevating the amount of serotonin in the brain. Serotonin is the contentment neurotransmitter, a chemical messenger in the brain that activates brain signaling associated with experiencing pleasure and feelings of well-being. The caveat is that for serotonin to be available for brain signaling, it must be on the outside of the brain’s cells, known as neurons. SSRIs work to inhibit the transporter that recycles serotonin by preventing the transport of serotonin back into the neurons from which it was released.

Antidepressants take so long to work because they inactivate not just individual serotonin transporters, but also the genes in our DNA that code for the transporter. The result over time is fewer serotonin transporters in the brain and more serotonin around to experience pleasant stimuli. SSRIs work better for some people than others because of individual variations in gene expression of the serotonin transporter. However, we do not yet have enough evidence to support the use of individual genetic testing to treat depression on a case-by-case basis. Additional variables that affect antidepressant response time include those related to drug metabolism: genetic differences in liver enzyme function, liver disease, age, sex, hormones, pregnancy, and nutritional status.

Length of Antidepressant Treatment

Antidepressants are prescribed not just to achieve maximum short-term relief of depressive symptoms, but also as a maintenance treatment to prevent future depressive episodes. Without treatment, a typical major depressive episode will last for approximately six months, has a 50% chance of recurring in six months and an 85% chance of recurring within a decade. For these reasons, antidepressant treatment is typically continued for at least six to twelve months after the resolution of depressive symptoms. In more severe cases, antidepressant treatment may be continued for up to three years, or indefinitely. 

Options for Improving the Effectiveness of Antidepressants

There are several treatment options to improve the effectiveness of antidepressants once an antidepressant has been tried for four to six weeks, including:

  • Increasing dosage: Antidepressants are started at low doses and then slowly increased. The dose is titrated up until relief of depressive symptoms is optimized and side effects of the drug are minimized.
  • Combining medication: When full relief of depressive symptoms is not achieved at the maximum dose of one antidepressant, another antidepressant or an atypical antipsychotic may be added for additional benefit.
  • Changing medication: Individuals may switch from one antidepressant to another when they receive no benefit from the first antidepressant or cannot tolerate its side effects. The first antidepressant must be tapered down before it can be completely discontinued.
  • Beginning concurrent psychotherapy: It is recommended that treatment with antidepressants be paired with psychotherapy for maximum benefit.
  • Engage in somatic treatments: Electrical stimulation of the brain is a common and effective treatment for depression. Common somatic treatments include electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). These treatments work by stimulating neurons in the brain that are responsible for mood and reality processing.

Esketamine for Faster Relief

Finally, for individuals with severe depression who have thoughts of suicide or are exhibiting life-threatening behavior, esketamine is recommended for faster relief. Esketamine, like ECT and rTMS, has a rapid onset of antidepressant action. Unique to esketamine, however, is its ability to significantly improve even the most severe of depressive symptoms within just a few hours or a day.

How does esketamine work so quickly? Esketamine acts on a stimulating neurotransmitter known as glutamate. Glutamate accounts for a significant majority of the brain’s neurotransmitters and may be largely responsible for most brain functions, including mood.

When to Talk to Your Doctor

If you are struggling with depression, visit your primary care provider, or establish care with one you trust. Working with an empathetic, compassionate and collaborative healthcare provider is an important first step in treating depression. The best care teams include a primary care provider, a case manager and a mental health specialist such as a psychiatrist. This kind of care has been shown to deliver the best treatment outcomes for people suffering from depression.

If you or a loved one struggle with depression and co-occurring addiction, The Recovery Village can help. You can receive comprehensive treatment for both conditions simultaneously from one of several facilities located throughout the nation. To learn more about depression and addiction treatment programs, call The Recovery Village to speak with a representative today. 

Megan Hull
Editor – Megan Hull
Megan Hull is a content specialist who edits, writes and ideates content to help people find recovery. Read more
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The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.