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

Treatment and Medication Options for Depression

Talk Therapy for Depression

• Behavioral Activation Therapy The aim of this type of therapy is to reverse the downward spiral of depression by encouraging you to seek out experiences and activities that give you joy.
• Cognitive Behavioral Therapy (CBT) CBT focuses on changing specific negative thought patterns so that you can better respond to challenging and stressful situations.
• Interpersonal Therapy This very structured, time-limited form of therapy focuses on identifying and improving problematic personal relationships and circumstances directly related to your current depressive mood.
• Problem-Solving Therapy This therapy is a form of CBT that teaches take-charge skills that help you solve real-life problems and stressors, both big and small, that contribute to depression.

Medication for Depression

• Selective Serotonin Reuptake Inhibitors (SSRIs) This category of drug includes fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and many others. They target serotonin, a neurotransmitter that helps control mood, appetite, and sleep.
• Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) SNRIs include drugs like 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 medications includes forms of bupropion (Wellbutrin).
• Tricyclic or Tetracyclic Antidepressants (TCAs) TCAs include such drugs as imipramine (Tofranil) and nortriptyline (Pamelor). These drugs were among the earliest antidepressants to come on the market. These days, doctors generally only turn to them 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’re rarely used today, in part because people who take them require careful monitoring to prevent negative interactions with certain foods and other medications.
• N-Methyl D-Aspartate (NMDA) Receptor Antagonists NDMAs help maintain the balance of glutamate and gamma-aminobutyric acid (GABA) in the body. They can help people whose symptoms haven’t been relieved by standard treatments and often work more rapidly than other antidepressants. They include drugs like esketamine (Spravato) and dextromethorphan-bupropion (Auvelity).
• Neuroactive Steroids Neuroactive steroids are believed to work by affecting GABA levels. They often work more rapidly than other antidepressants.

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   They include drugs like brexanolone (Zulresso) and zuranolone (Zurzuvae), which are both FDA-approved to treat postpartum depression.

• Serotonin Receptor Agonists This new class of antidepressants is thought to work by affecting certain serotonin receptors in the brain that help regulate mood and emotions. This class includes the drug gepirone ER (Exxua).

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• Nausea
• Headache
• Drowsiness
• Diarrhea
• Upset stomach
• Dry mouth
• Weight gain
• Sexual problems

In addition, it may take some patience before you see results. The full benefits of the drugs may not be realized until you’ve taken them for as long as three months.

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

If your depression isn’t improving enough with standard treatments, or if symptoms of psychosis (having delusions or seeing or hearing voices that are not real, for example) are present, a doctor may prescribe an antipsychotic medication.

Should You Worry About Antidepressant Withdrawal?

What Is Treatment-Resistant Depression, and Is There Any Help for It?

It is not, however, a hopeless condition. A number of treatment approaches for TRD are available, including:

• Esketamine (Spravato) A nasal spray, Spravato won FDA approval on March 5, 2019, as a new treatment for TRD. It is derived from ketamine, a veterinary anesthetic best known as the street drug “Special K.” Because of safety concerns, Spravato must be administered in a medical office and can be taken on its own or in combination with an oral antidepressant.

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• Electroconvulsive Therapy (ECT) ECT involves a brief electrical stimulation of the brain while the patient is under anesthesia. ECT rapidly provides substantial improvement in approximately 80 percent of patients with severe, uncomplicated major depression.

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   Like any medical procedure, ECT is associated with side effects — mainly issues with memory. In most cases, this is a short-term issue; however, some people can experience permanent gaps in memory.

• Transcranial Magnetic Stimulation (TMS) TMS uses rapidly alternating magnetic fields to change activity in specific areas of the brain. Although researchers don’t fully understand exactly how TMS affects the brain, it appears to influence how the brain is operating and, in turn, improves mood and decreases depressive symptoms.
• Vagus Nerve Stimulation This therapy involves implanting a tiny device in the chest that provides regular mild electrical pulses to the longest of the nerves that arise from the brain. Vagus nerve stimulation has been found to significantly improve quality of life for many patients.
• Psychedelic Drugs While not yet approved by the FDA, microdosing with psychedelic drugs to produce a more positive mood in people with chronic depression is the focus of a flurry of research worldwide. Evidence has yet to endorse the use of psychedelics for the treatment of any mental health condition except during approved investigational studies, and more research is needed in this field.