What Is Depression (Major Depressive Disorder, or MDD)?

Depression Treatment and Medication Options

If you suspect that depression is interfering with your life, it is essential to talk about what you are experiencing and discuss treatment options with a medical professional. There is abundant evidence that people with depression who seek treatment find significant relief with talk therapy, medication, lifestyle changes, or a combination of these.

Talk therapy for depression

Several types of psychotherapy have been shown to be effective in treating depression, including:

behavioral activation therapy The goal of this type of therapy is to reverse the downward spiral of depression by encouraging you to seek out experiences and activities that bring you joy.
Cognitive behavioral therapy (CBT) CBT focuses on changing specific negative thought patterns to help you cope better with difficult and stressful situations.
interpersonal therapy This highly structured, time-limited therapy focuses on identifying and improving problematic relationships and situations that are directly related to your current depressed mood.
problem solving therapy This therapy is a type of CBT that teaches take-charge skills that help you resolve real-life problems and stressors, large and small, that contribute to depression.

drugs for depression

Antidepressants cause chemical changes in the brain that affect how neurons communicate. Exactly how this improves mood remains a mystery, but the fact that it often works is well established. If you’re thinking of trying antidepressants, talk to your doctor about whether these treatments are right for you.

Selective serotonin reuptake inhibitors (SSRIs) Drugs in this category include fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft). They target serotonin, a neurotransmitter that helps control mood, appetite, and sleep.
Serotonin and noradrenaline reuptake inhibitors (SNRIs) SNRIs include drugs such as duloxetine (Cymbalta), desvenlafaxine (Pristiq), and venlafaxine (Effexor XR), which block the reabsorption of both serotonin and another neurotransmitter, norepinephrine.
Norepinephrine-dopamine reuptake inhibitors (NDRIs) This class of drugs includes forms of bupropion (Wellbutrin).
Tricyclic or tetracyclic antidepressants (TCAs) TCAs include drugs such as imipramine (Tofranil) and nortriptyline (Pamelol). These drugs were among the earliest antidepressants to hit the market. These days, doctors are only seen when treatment with SSRIs, SNRIs, and NDRIs has failed.
Monoamine oxidase inhibitors (MAOIs) MAOIs, including phenelzine (Nardil) and isocarboxazid (Marplan), were the first antidepressants developed. They are now rarely used because the person taking them must be closely monitored to prevent adverse interactions with certain foods and other medications.
N-methyl D-aspartate (NMDA) receptor antagonist NDMA helps maintain the balance of glutamate and gamma-aminobutyric acid (GABA) in the body. It can help people whose symptoms have not been relieved by standard treatments, and it often works more quickly than other antidepressants. These include drugs such as esketamine (Spravato) and dextromethorphan bupropion (Auvelity).
neuroactive steroids Neuroactive steroids are thought to work by affecting GABA levels. It often works faster than other antidepressants. These include drugs such as brexanolone (Zulresso) and zuranolone (Zurzuvae), which are approved by the FDA to treat postpartum depression.
Serotonin receptor agonist This new class of antidepressants is thought to work by affecting specific serotonin receptors in the brain, which help regulate mood and emotions. This class includes the drug gepirone ER (Exxua).

All antidepressants can have side effects, but some antidepressants can be more problematic than others. You may need to try several different medications (or a combination) under your doctor’s guidance to find what’s best for you. The most common side effects of antidepressants include:

nausea
headache
sleepiness
diarrhea
upset stomach
dry mouth
weight gain
sexual problems

Also, it may take some patience to see results. The full effects of the medicine may not be felt until you have taken it for up to 3 months.

Other medications may be added to your regimen, depending on the form of depression, severity of symptoms, and response to other treatments. These may include mood stabilizers such as lithium (sold under several brand names) and valproic acid (Depakene, Depakote).

Doctors may prescribe antipsychotic drugs if depression does not improve sufficiently with standard treatments or if people have symptoms of psychosis (such as having delusions or seeing or hearing voices that are not real).

Some experts believe that using antipsychotics in combination with antidepressants may be more effective against depression than antidepressants alone. Antipsychotics that are approved for use with antidepressants include lumateperone (Caplyta), brexpiprazole (Rexulti), aripiprazole (Abilify), cariprazine (Vraylar), quetiapine (Seroquel XR), and fluoxetine and olanzapine (Symbyax).

Should I be concerned about antidepressant withdrawal?

In general, stopping antidepressants is safe as long as the dose is slowly reduced with the help of a doctor. Antidepressant discontinuation syndrome (ADS) can occur when a drug is suddenly stopped without being tapered. ADS is characterized by a wide range of reactions, including but not limited to flu-like symptoms, insomnia, worsening mood, and nausea.

One study concluded that approximately 15 percent of patients who discontinue antidepressants develop symptoms. Only about 3% have severe symptoms.

What is treatment-resistant depression? Is there a way to solve it?

If your depression does not improve after trying at least two antidepressants, you may be diagnosed with treatment-resistant depression (TRD). TRD is a serious condition that is closely associated with suicidal thoughts and attempts. Thirty percent of patients with treatment-resistant depression attempt suicide during their lifetime, twice as many (15%) as patients with treatment-responsive depression.

But it’s not a hopeless situation. A variety of treatment approaches are available for TRD, including:

Esketamine (Supravat) Spravato, a nasal spray, received FDA approval on March 5, 2019, as a new treatment for TRD. It is derived from ketamine, an animal anesthetic best known as the street drug “Special K.” Due to safety concerns, Supravat must be administered in a doctor’s office and can be taken alone or in combination with oral antidepressants.
Electroconvulsive therapy (ECT) ECT involves delivering brief electrical stimulation to the brain while the patient is under anesthesia. ECT produces rapid and significant improvement in approximately 80% of patients with severe, uncomplicated major depression. Like any medical procedure, ECT is associated with side effects, primarily memory problems. In most cases, this is a short-term problem. However, some people may experience permanent gaps in their memory.
Transcranial magnetic stimulation (TMS) TMS uses rapidly alternating magnetic fields to change the activity of specific areas of the brain. Although researchers don’t understand exactly how TMS affects the brain, it appears to affect how the brain operates, thereby improving mood and reducing symptoms of depression.
vagus nerve stimulation This treatment involves implanting a small device in the chest that periodically delivers weak electrical pulses to the longest nerve originating from the brain. Vagus nerve stimulation has been shown to significantly improve the quality of life for many patients.
psychedelic drugs Although not yet FDA-approved, microdosing psychedelic drugs to create a more positive mood in chronically depressed patients is the focus of a flurry of research around the world. There is still no evidence to support the use of psychedelic drugs to treat mental health conditions, except during approved clinical trials, and more research is needed in this area.