For most patients looking for depression relief with typically prescribed antidepressants, the standard waiting time is four to six weeks just to see a glimmer of light through their symptoms. That is if the medication they are trying works at all. Many times the patient needs to trudge through various medications to see which one will both be effective for them and have tolerable side effects.
This trial and waiting period of potentially several months can be exhausting for those already in the depths of the hopelessness and despair of severe depression. To make matters worse, up to thirty percent of patients with major depressive disorder (MDD) do not respond to treatment with current medications. Thus, mental health professionals have been searching for an effective tool to rapidly alleviate the symptoms of MDD. Apart from the potentially memory-damaging electroconvulsive therapy, there are limited options for rapid and dramatic relief.
Ketamine is a general anesthetic, tranquilizer, and dissociative party drug that doctors have known for years can temporarily alleviate depressive symptoms in as little as one treatment. An analysis of various clinical trials suggested that 50-70% of subjects with treatment resistant depression (TRD) responded to a single dose low dose intravenous (IV) ketamine infusion. The decrease in depressive symptoms only 2 hours after the first infusion has been shown to be dramatic and sustained in a study that administered 6 infusions over a 12 day period.
The problem with ketamine is that it was never approved by the FDA to treat depression. It has not been shown to be both safe and effective in the long term. As a result most insurance companies will not cover treatment. The expense of the in-office IV infusions puts it out of reach for most patients ($300-$1300 per infusion with 6 initial infusions needed).
The FDA needs quality research to approve a drug to treat a specific diagnosis and to test it for safety. With nearly 50 years on the market (ketamine was approved in the US in 1970), no company would pay for costly research and an FDA review process for a drug that they cannot patent.
Esketamine, the industry’s solution
In order to make a return on their investment, Janssen Pharmaceutica needed to find a drug with similar properties but without the patentability dilemma. They found an option quickly: one half of the ketamine molecule esketamine (known chemically as
S(+)-ketamine). Esketamine has been known as a stronger anesthetic with fewer side effects than ketamine since 1997. Janssen, a Johnson & Johnson company, needed to show that it was safe and effective for depression.
In 2013 the FDA granted breakthrough therapy designation for the drug to treat TRD. Breakthrough therapy designation allows for a faster review process for potentially lifesaving medication. After six phase III trials and a recommendation by an expert review panel, the FDA approved the drug for the US market on March 5, 2019. The approval is not without controversy however. The real long term safety is unknown and there are concerns about potential dependence and abuse. Esketamine (marketed under the brand name Spravato) is only approved as a nasal spray for adult patients with depression taking at least one antidepressant. Furthermore, due to its side effects and potential for abuse, it must be administered in an DEA approved doctor’s office.
Ready to treat
Janssen says it already has “up to 800 sites certified” to administer the treatment. Patients will receive 56 mg or 84 mg intranasal doses two times a week for the first month. Janssen will charge the clinic from $590 – $885 for the cost of the medication. It is unknown what the end cost will be for patients due to differences in insurance plans and the prices that the clinics will charge for the service. The VA, desperate to curtail it’s mental health problem, will also offer Spravato to veterans that meet certain criteria.
It remains to be seen how effective and safe esketamine will be over the long term. Brain scans suggest that damage from ketamine abuse may be possible, although no long term scans from the lower doses used to treat depression have been done. The FDA approval decision most likely took patient suicide into account. The risks versus possibly being able to stem suicides in a vulnerable population was a probable motivating factor. For now we can only wait to see if the long-awaited treatment lives up to it’s hype.