Managing Depression


“I found that with depression one of the most important things you could realize is that you’re not alone. You’re not the first to go through it; you’re not going to be the last to go through it… I wish I had someone at that time who could just pull me aside and say, ‘Hey, it’s gonna be okay. It’ll be okay.’”  -Dwayne “The Rock” Johnson

Many people experience depression over the course of their lives. Major Depressive Disorder (a “clinical” level of depression) is one of the most common mental disorders in the U.S. At any given time, approximately 1 out of 14 Americans suffer from the disorder. In addition to depressed (and/or irritable) mood, Major Depressive Disorder is also associated with changes in sleep, appetite, energy, enjoyment, concentration, and motivation. Depression can lead to feelings of hopelessness, guilt, low self-esteem, anxiety and thoughts of suicide. Depression is a treatable illness.

The early 1900s was a time of significant exploration into chemicals that might be useful to treat psychiatric disorders, resulting in a psychopharmacologic “revolution” in the mid 1950s.  The 1950s saw the introduction of chlorpromazine (Thorazine) for schizophrenia, the reintroduction of lithium carbonate for mania, and even exciting research into the therapeutic effects of LSD and psilocybin.  The first modern antidepressants (isoniazid and imipramine) were discovered by serendipity. Isoniazid was first studied as a treatment for tuberculosis and then found to have unexpected antidepressant properties; a photograph was published showing patients in a TB sanitarium dancing happily, and Dr. Nathan S. Kline, a psychiatrist, wrote of “a sense of joyousness and optimism” in TB patients who took it. Imipramine was discovered in attempts to alter the structure of chlorpromazine to create a more effective antipsychotic; instead, it improved mood. In the decades since, many more antidepressants have come on the market, most with fewer side-effects.  

Scientists, in studying these chemicals to figure out how and why they affect mood, developed the hypothesis that depression is caused by “chemical imbalances” in neurotransmitter systems such as serotonin and norepinephrine. However, the story is much more complex, and we are still not sure what causes depression or exactly how the medications work. 

Most psychiatrists and other physicians who prescribe medications for depression and anxiety agree, however, that medications are only one of many options to consider and ideally in the context of a full assessment of contributory factors. And when used, they work best in combination with other strategies, such as psychotherapy and attention to lifestyle factors (sleep, exercise, nutrition, engaging in activities of interest, relaxation, positive social connections, spending time in nature, and minimizing substance use). In fact, the evidence shows that psychotherapy is equally effective for mild-to-moderate depression as antidepressant medications.  

However, for moderate-to-severe depression, medication plus psychotherapy appears to be significantly more effective than either alone. Signs of moderate-to-severe depression include having a larger number of symptoms, impairment in functioning (at home, work, school, and in relationships), a higher level of distress, loss of interest/enjoyment, hopelessness, and suicidal thinking.  

The medications we currently use to treat depression are far from perfect. They don’t work for all people, and all medications have side-effects and potential risks. There are many different antidepressants, divided into several “families,” based on their neurotransmitter effects. In general, the antidepressants are equally effective across the population, but one might work better than another for a specific person. Choosing a medication to start with can be guided by the person’s past response to a medication, a close family member’s experience on a medication (a genetic “clue”), the medication’s side-effect and risk profile, and the type of depression. If the first medication doesn’t work well or leads to intolerable side-effects, strategies include adding another medication, adding psychotherapy, or switching to something different. For example, adding low-dose lithium can be helpful for anti-suicide and antidepressant effects. It is also important in these situations to consider if something was missed, such as a thyroid condition, PTSD, substance use or bipolar disorder. 

Most of the antidepressants used today have complex effects on several different neurotransmitter systems such as the serotonin, norepinephrine, and dopamine receptors and pathways. Again, we don’t fully understand how they work. Older antidepressants include the tricyclic antidepressants (TCA’s, such as Imipramine) and the monoamine oxidase inhibitors (MAOI’s, which require dietary restrictions).  They are at least as effective as the newer medications, but cause more side-effects.  The most commonly prescribed of the “newer” medications are the selective serotonin reuptake inhibitors (SSRI’s, such as Prozac, Zoloft and Lexapro). Other antidepressant “families” include the serotonin norepinephrine reuptake inhibitors (SNRI’s such as Effexor and Cymbalta), Remeron, and Wellbutrin. Most antidepressants also reduce anxiety, which is fortunate, since anxiety and depression often occur together. 

The antidepressants take a while to kick in. After about two weeks of daily medication, one hopes to see some symptoms beginning to improve, and it can be subtle at first. To assess full effectiveness at a certain dose, it can take closer to six weeks. Side-effects often resolve over a few days, so with mild side-effects, it’s important to try and stick it out. Common side-effects can include upset stomach/nausea, headaches, jitteriness in the short term, insomnia or sedation, and dry mouth. Sexual side-effects (such as decreased libido) are common for the SSRI’s and may or may not resolve over time on the medication. Side-effects can be managed by giving them time to resolve, dose reduction, changing the timing of the dose, adding something to address the side-effect, or switching to a different medication. 

The FDA has placed a “black box warning” on all antidepressants describing rare case reports of the development of suicidal thoughts, especially in adolescents and young adults. While it is important to monitor for that, untreated depression itself is a significant risk for suicide. 

Another risk is that people with bipolar disorder (diagnosed or not yet diagnosed) can get worse with antidepressants, so it’s important to assess carefully for that. This is especially relevant if there is any family (genetic) history of bipolar disorder.

People often wonder how long they should stay on an antidepressant. If the medication is working and side-effects are not a problem, staying on the medication for at least 12 months significantly lowers the risk of the depression returning. Engaging in psychotherapy also lowers the risk of recurrence. If someone has had more than one episode of depression (“recurrent depression”), the risk of having further episodes is very high if an effective medication is stopped, so it might be prudent to stay on the medication longer term.

Newer research and medications are now targeting other neurotransmitter systems, such as melatonin (Agomelatine) and glutamate/NMDA receptors (ketamine, esketamine), as well as anti-inflammatory agents and psychedelics. There is strong interest in ketamine/esketamine to treat depression because of its significantly faster onset of action, especially for people struggling with severe depression and suicidal thinking; risks include addiction, dissociative experiences, and questions about short duration of effectiveness. 

Non-medication “somatic” treatment strategies for more serious depression, or when medications and psychotherapy aren’t effective, include transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT). More information about these can be found on the websites listed below.

The important thing is to work closely with a mental health/medical provider you feel comfortable with, ask a lot of questions, weigh the risks and benefits of different options, and communicate openly about symptoms, side-effects and the treatment plan. It is crucial to tell your treatment providers about anything else you might be taking, including over-the-counter medications, herbal supplements, alcohol, and any recreational drugs. This helps to avoid risky drug interactions and identify other influences on recovery. The experience of depression is different for each person, and so is the treatment; the most effective approach is individualized and strongly guided by personal goals, values and preferences.

Here are some reputable resources for more information about depression and its treatment: /topics/depression/index.shtml;

If you or someone you know is experiencing suicidal thoughts, the National Suicide Prevention Lifeline at 1-800-273-TALK (1-800-273-8255) is available 24/7 for immediate help. Use that same number and press “1” to reach the Veterans Crisis Line.  For an emergency, call 911.  


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