New antidepressants can lift depression and suicidal thoughts fast, but don’t expect magic cures

Long-term relief from major depression involves more than just drugs. Rafa Elias via Getty Images
Depression is the leading cause of disability worldwide. Chances are that you or someone you know is going through a time when depression is affecting work, social life, or family life. Almost two in three people with depression have serious effects.
As a behavioral neuroscience psychiatrist, I help patients suffering from mood disorders. Many suffer from "treatment-resistant" depression and are almost constantly in search of relief.
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There have been some exciting developments in the treatment of depression recently, especially new fast-acting antidepressants. However, it is important to understand that these drugs are not a panacea.
The new treatments for depression promise to relieve distressing symptoms, including thoughts of suicide, faster than any previous treatment. These include ketamine, an anesthetic also used as a street drug, and a derivative of ketamine called esketamine. These drugs have been shown to relieve symptoms of depression in hours, but each dose is only effective for a few days. They also carry risks, including the potential for substance abuse.
With the coronavirus pandemic affecting mental health, patients are looking for quick relief. Medication can help, but more than medication is required to effectively treat depression, with its mix of biological, psychological, social, and cultural components in the long term.
Depression drugs have evolved
The early history of treatment for depression focused on the psychological components of the disease. The goal at the beginning of the 20th century was for a patient to understand unconscious needs during childhood.
Biological treatments at that time seem scary today. These included insulin coma therapy and primitive, often-abused versions of a modern life-saving technique - electroconvulsive therapy.
In the middle of the 20th century, drugs were discovered that influenced behavior. The first drugs were sedatives and antipsychotics. Chlorpromazine, marketed as "Thorazine", was a leader in the 1950s. Imipramine was discovered in 1951 and became one of the first antidepressants. The blockbuster antidepressant Prozac, a selective serotonin reuptake inhibitor (SSRI), was approved in 1987.
The doctor-patient relationship can help manage all of the components of major depression. SolStock via Getty Images
It has been over 30 years since we saw a novel class of antidepressants. This is one of the reasons fast-acting antidepressants are exciting.
How depression looks in the brain
Medical treatments for depression affect certain processing cells in the brain area above your eyes and under your forehead. This area, called the prefrontal cortex, processes complex information, including emotional expressions and social behavior.
Brain cells called neurons are chemically controlled by two opposing messenger molecules, glutamate and gamma-amino-butyric acid (GABA). Glutamate acts like an accelerator pedal and GABA is the brake. You tell the neurons to speed up or slow down.
Fast-acting drugs for depression reduce the effects of glutamate, the accelerator pedal.
Other treatments have been developed to rebalance GABA. A neurosteroid called allopregnanolone affects GABA and applies the brakes. Both allopregnanolone and esketamine are federally approved for the treatment of depression, allopregnanolone for postpartum depression and esketamine for depression and thoughts of suicide.
Not so fast
Between 2016 and 2017, young psychiatrists like me rushed to implement these novel antidepressants. Our trainers said, "Not that fast." They explained why we should wait and see how the studies of the new drugs develop.
A few years earlier, the medical community was similarly excited about Vivitrol to treat opioid addiction. Vivitrol is a monthly injected form of naltrexone, an opioid-blocking medicine.
Clinical trials are conducted in a highly controlled and clean environment, while the real world can be very uncontrolled and very chaotic. Without risk mitigation, education, and psychosocial treatment, the potential risks of drugs like Vivitrol can be increased. Vivitrol can help reduce relapses but is not a panacea in itself. The National Institute for Drug Abuse recommends integrated addiction treatment.
Treatment for depression can be similar. Medication and psychological support work better together than either alone.
The risks
The more treatments a person tries for depression that doesn't work, the less likely that person is to succeed with the next treatment option. This was a key message of the largest clinical trial investigating depression medication, the National Institutes of Health's STAR-D study, completed in 2006.
Providing a more effective option for patients who are unresponsive to a first or second antidepressant can turn this STAR-D message on its head. However, if it is a disease that is affected by external stress such as trauma and loss, then treatment with both medication and psychological support is more likely to be effective.
A real-world treatment approach called the bio-psychosocial paradigm takes into account the wide range of relevant biological, psychological, and social components of mental illness. The patient and doctor work together to process the patient's problematic experiences, thoughts, and feelings.
Hyperfocus on novel drugs could overlook the importance of addressing and monitoring all of these components, which could mean problems will arise in the future. Drugs such as opiates or other substances that provide rapid relief from physical or mental pain can also be physically and psychologically addicting, and novel fast-acting antidepressants can have the same risks.
Fast-acting antidepressants, when used in other forms of therapy, can be an effective tool for treating severe depression. However, are they the answer? Not so fast.
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This article was republished by The Conversation, a non-profit news site dedicated to exchanging ideas from academic experts. It was written by: Nicholas Mischel, Wayne State University.
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Nicholas Mischel has received or has received funding from the American Heart Association, the National Institutes of Health, and Wayne State University. He is employed at Wayne State University and is a member of the American Psychiatric Association, the Society of Biological Psychiatry, the North American Neuromodulation Society, the Clinical TMS Society, and the American Society of Ketamine Physicians, Psychotherapists & Practitioners.

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