If you want to know whether a standard-of-care medication will work to treat your depression, flip a coin.
More than half of all patients treated for major depressive disorder (MDD), the clinical name for what is typically thought of as depression, don’t respond to the first treatment option prescribed to them. Even those who do respond often won’t see the full clinical benefit for up to 12 weeks. And yet, prescribing these medications is standard practice in a field that adheres to a “start low, go slow” approach to medication therapies.
I believe that this approach is outdated and no longer serves patients, more than 50 percent of whom require multiple therapeutic approaches before finding one that works for them.
People are suffering. We can do better.
Non-pharmacologic interventions, such as electroconvulsive therapy and transcranial magnetic stimulation, work more quickly than medications, and many have longer-lasting effects. Meanwhile, clinical trials involving investigational agents such as psilocybin are showing promise, and off-label or approved use of drugs such as ketamine and esketamine are delivering fast, long-lasting results to patients for whom standard-of-care medications have not worked. The consequence of not having rapid effects on depression include the risk of suicide, not taking the right medication that could help, treatment costs, and greater disease burden.
In a paper I published recently in the journal CNS Spectrums, I noted that the most significant downside to any of these alternatives is the fact that all must be administered in a facility by trained specialists, which adds to the time to treatment.
However, the fast-acting results of these alternatives suggest that there are better, safer methods out there to help people with MDD. And discovering those better alternatives is critical.
MDD is characterized by a host of undesirable symptoms, including:
- anhedonia or decreased interest in pleasurable activities
- feelings of guilt or worthlessness
- lack of energy
- poor concentration
- appetite changes
- slowing down of thought and/or movement
- sleep disturbances
- suicidal thoughts.
Delays in symptom resolution are associated with poor outcomes and decreased quality of life. These effects are not trivial: MDD accounts for 87 percent of suicides, and MDD is one of the leading causes of disability worldwide. Meanwhile, when treatment does work soon after diagnosis, patients experience a greater likelihood of recovery. So, getting treatments that work as quickly as possible is essential.
Clearly, an unmet need exists for innovative treatments that offer rapid and sustained effects, and I’m excited by some of what I am seeing in our field. Innovative treatments are now emerging, and continued investigational work in this area will allow doctors to cater to individualized therapy that works quickly and provide the help people need when they need it.
Electroconvulsive therapy (ECT), which involves applying electrical stimulation to a patient’s brain, is an FDA-approved intervention associated with fast and sustained effects in patients with severe treatment-resistant depression. Another exciting treatment option is transcranial magnetic stimulation (TMS), also an FDA-approved, rapid-acting, non-pharmacologic therapy that treats adults for whom standard medications have failed.
Drugs with rapid and sustained effects that are now approved or used off-label include ketamine, esketamine, and dextromethorphan-bupropion, which can provide antidepressant effects as quickly as one hour after taking them – with effects sustained for up to six weeks. However, ketamine and esketamine both carry the potential for abuse, and all three require in-clinic visits for treatment.
Psychedelics, such as psilocybin, are also showing promise in clinical trials for patients whose MDD symptoms have not been relieved by standard medications.
I am excited to see the therapeutic landscape for MDD shifting to better address the delay in relief patients have experienced. We are on the cusp of something powerful, meaningful, and lasting. Something that will turn the “start low, go slow” clinical approach into a more effective mindset that recognizes time is of the essence when treating depression.
It is my hope that the work being done in this field will yield therapies that target individualized treatments to provide relief quickly and effectively because MDD is debilitating, and the odds of you recovering from it should be greater than the toss of a coin.
Gus Alva is a psychiatrist, Hoag Memorial Hospital Presbyterian.