By Lenny Salzberg, M.D.
In 1987, a revolutionary new treatment of depression was introduced. Prozac® (fluoxetine) is an effective antidepressant with fewer side effects than the medications we formerly used to treat depression. Prozac was the first in a new class of medications called “Selective Serotonin Reuptake Inhibitors (SSRIs)”. Four years later, in 1991, Zoloft® (sertraline) was introduced. Then, a year later, Paxil® (paroxetine) became available.
The medications I learned about in medical school to treat depression were called tricyclic antidepressants (like Nortriptyline, otherwise known as Pamelor), and Monoamine Oxidase Inhibitors (MAOIs). In the years since SSRIs were introduced, they (and another class of medications called SNRIs) have almost completely replaced TCAs and MAOIs in primary care doctors’ toolbox for the pharmaceutical treatment of depression.
Not only do SSRI’s tend to have fewer side effects than TCAs and MAOIs, they are also much safer. As a young doctor I admitted many patients to the Intensive Care unit after they overdosed on less than a month’s supply of their TCA or MAOI medications. Most of these patients made it, but some did not. In contrast, it’s very hard to overdose on an SSRI. Even if you took a 90-day supply of an SSRI all at once, you probably would not die.
SSRIs work well for people with severe depression. They work even better when combined with counseling and exercise. They do not, however, work for everyone. Sometimes people have “treatment-resistant depression”, which is defined as a major depressive disorder that has not responded adequately to two or more different antidepressant regimens of adequate dose and duration.
Until recently, when I’ve had patients with treatment-resistant depression, I’ve tried augmenting their antidepressant with other medications (with antipsychotic drugs, lithium, or triiodothyronine). I’ve also referred patients to psychiatrists for electroconvulsive (shock) therapy or transcranial magnetic stimulation (which uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression). More recently, there have been trials with deep brain stimulation, which is a new technique that has proved effective for a small number of patients. However, for the most part, my patients and I have been frustrated about the lack of good options for treatment-resistant depression.
In 2019, a revolutionary new treatment of depression was introduced. Spravato® (esketamine nasal spray) is an effective antidepressant for treatment-resistant depression in adults.
Spravato must be administered under the direct supervision of a healthcare professional. The drug is administered through a nasal spray, and it comes in a kit containing two 56 mg doses and three 84 mg doses. The first dose is 56 mg, with subsequent doses being either strength. Patients should be monitored for 2 hours after taking the dose and should then be escorted home. Doses are given twice weekly for four weeks, then once weekly for four weeks, then once weekly or every other week thereafter. Blood pressure needs to be closely monitored, as this medication can lead to a hypertensive emergency. Studies are promising. In other words, this seems to be a good treatment option for treatment-resistant depression. I have many patients who will benefit from this (as soon as I find who is administering this therapy in our region).
Depression is very common, affecting 8% – 10% of people in the United States, and as many as 20% of patients that come to physicians’ offices. As a Family Physician, I routinely see patients with depression. Depression and chronic diseases (e.g. diabetes, heart disease, and pain syndromes among others) frequently coexist and have a bidirectional relationship. That is, being depressed makes you more likely to have a chronic disease, and having a chronic disease makes you more likely to be depressed. Treatment for depression usually involves taking medications for months and sometimes years. However, as mentioned above, the best antidepressants don’t work for everyone.
There are many risk factors for depression. Some of these are internal factors (e.g. female gender, history of anxiety, low self-esteem); while some relate to adverse live events (e.g. childhood sexual abuse, chronic medical conditions, divorce, poor social support, loss of a parent). Risk factors for late-life depression include social isolation, the death of a spouse, uncontrolled pain, and cognitive and functional impairments (like dementia). Depression is a major risk factor for suicide in older men, with suicide rates increasing with age.
The United States Preventive Services Task Force (USPSTF) and the American Academy of Family Physicians (AAFP) recommend that I screen for depression in all of my adult patients. I do this in my office with the Patient Health Questionnaire Screening Instrument for Depression (PHQ-9). This nine-question screening test asks how often, over the past two weeks, you have been bothered by any of these problems:
- Little interest or pleasure in doing things
- Feeling down, depressed, or hopeless
- Trouble falling or staying asleep, or sleeping too much
- Feeling tired or having little energy
- Poor appetite or overeating
- Feeling bad about yourself or that you are a failure or have let yourself or your family down
- Trouble concentrating on things, such as reading the newspaper or watching television
- Moving or speaking so slowly that other people could have noticed, or the opposite – being so fidgety or restless that you have been moving around a lot more than usual
- Thoughts that you would be better off dead or of hurting yourself in some way
If you endorse at least five of these, you may have mild depression. Endorsing more than five may indicate moderate depression, with higher scores correlating with more severe depression.
Screening tests imply that you may be depressed. I then need to confirm the diagnosis with a clinical interview. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines depression as either depressed mood or anhedonia (little interest in doing things), plus at least four other symptoms asked about in the PHQ-9, for at least two weeks. I pay particular attention to the question about “feeling better off dead”. If patients answer that they feel this way every day, it prompts me to investigate even further. Sometimes this is an emergency that requires hospital admission.
We screen for depression because it is a common, TREATABLE, serious illness. With therapy and medication we can make a difference in your life.