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Another depression medication proves riskier than the disease itself: Researchers recommend an “immense amount of caution” due to side effects
By Cassie B. // Nov 14, 2019

When you’re in the throes of depression, you might be willing to try anything to make the feelings stop. Many sufferers turn to medication while waiting for longer-term solutions like therapy to have an effect, and while this may indeed take the edge off temporarily, it could come at a very steep price when it comes to your health.


The latest example is esketamine, a drug that is currently being tested to help treat severe depression quickly. A form of ketamine, which is used as an anesthetic, esketamine has been shown to reduce severe depression symptoms like suicidal ideation quickly in some patients – which might even mean the difference between life and death in some cases.

Although a randomized, placebo-controlled, double-blind study found that a nasal spray of esketamine worked well where traditional antidepressants had failed, the authors cautioned that unwanted side effects like psychosis and depersonalization could occur without a proper risk assessment.

The study involved more than 200 adults suffering from moderate to severe depression who had failed to respond to at least two antidepressants. The participants were from 39 different outpatient referral centers in the U.S., Spain, Germany, Poland and the Czech Republic. They were followed for the course of approximately two years.

The researchers divided the patients into two groups, one of which was given twice weekly doses of esketamine, while the other group was given a placebo nasal spray. All participants were also given an antidepressant they had not previously taken, such as sertraline, escitalopram, duloxetine, or extended-release venlafaxine.

After four weeks, those who had taken the esketamine spray had significantly higher improvements in their depression than those in the placebo group. This supports the idea that the treatment is effective.

However, the people in the esketamine group also suffered from symptoms of dissociation and effects on perception. These effects were noted shortly after the drug was administered and peaked around 40 minutes later. Although the symptoms resolved after around an hour and a half and occurred less frequently as the treatment continued, it’s still a major cause for concern.

Other side effects commonly experienced by participants taking the esketamine included vertigo, dizziness, nausea, and changes in their sense of taste. The adverse effects were strong enough to prompt 7 percent of participants taking esketamine to drop out of the trial entirely.

Experts urge caution

That’s why many researchers are calling for caution with this drug. The FDA has already given an esketamine nasal spray its nod of approval for treating severe depression alongside orally administered antidepressants, albeit only in adults who haven’t had success with other forms of treatment. However, some experts disagree with this decision.

One scientist who was not involved in the study, Stanford University School of Medicine’s Dr. Alan Schatzberg, wrote in a commentary accompanying the study paper that the drug has the potential for misuse and abuse, adding that there are still a lot of things we don’t know about it.

Although he conceded that a nasal spray is an easier way of giving people ketamine than intravenous delivery, he said its efficacy was only mild and we don’t have a clear sense of how long and how often it should be prescribed. He urged caution in using the drug and said that we have more questions than answers here.

Kaiser Health News recently reported that the manufacturer of nasal esketamine spray Spravato, Janssen, did not provide the FDA with any information on the drug’s safety in long-term use past 60 weeks. Moreover, they pointed out that three patients who were given the drug in clinical trials died by suicide, versus none in the control group, and the pharmaceutical firm and the FDA both ignored this huge red flag.

Despite initial hope, it’s becoming increasingly clear that this is yet another depression medication that is riskier than the disease itself. Everyone’s depression is different, but it’s worth trying non-medical interventions like talk therapy, exercise, dietary improvements and meditation before taking on the potentially life-threatening risks of depression medication.

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