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Can Antidepressants Work for Me?

Reviewed by Michael W. Smith, MD on April 09, 2021

Antidepressants are a common way to treat depression. But they work a little differently for everyone. That may leave you wondering if they’ll work for you.  

Who Do Antidepressants Work Best For?

There’s no clear-cut answer. But there’s growing evidence that antidepressants work better than placebo (a "fake" drug) for most everyone who takes them.

But you might’ve heard that they’re more effective for people with serious depression.

Gerard Sanacora, MD, director of the Yale Depression Research Program, says the research has a bit of nuance. He says it’s not so much that antidepressants work better for people with serious depression.

"It’s that the antidepressants work better when compared to placebo, which is a little tricky," he says. "It means that, with the less severely depressed, placebos work pretty darn well." 

Another way to look at it is: If you have mild symptoms, you’re likely to get better with other options.

"It could be well worth trying a nondrug treatment first, such as cognitive behavior therapy [CBT] or another psychotherapy," Sanacora says. 

Choosing the Right Antidepressant

Experts generally don’t know which one will work best.

"It would be nice if we had this simple algorithm that showed this one is more effective than that one," Sanacora says. "But we don’t have that. It really is variable." 

With that said, he says most doctors generally take the same approach.

Your treatment may include: 

Selective serotonin reuptake inhibitors (SSRIs). These work on a single neurotransmitter -- a chemical messenger between nerve cells -- called serotonin. SSRIs are usually the first thing your doctor will try. There are several reasons why.

"They tend to be well-tolerated, and it’s an inexpensive medicine," Sanacora says. "And we also have 30 years of safety data."

Commonly used SSRIs include:

  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)

Selective serotonin and norepinephrine reuptake inhibitors (SNRIs). These work on two neurotransmitters: serotonin and norepinephrine. Sanacora says there’s some evidence that SNRIs may be more effective than SSRIs for some people.

"But my ability to predict that for one person is not very strong," he says.  

Continued

You may not have any problems with SNRIs. But Sanacora says they’re usually a second choice because they tend to have more side effects.

Commonly used SNRIs for depression include:

  • Desvenlafaxine (Pristiq)
  • Duloxetine (Cymbalta)
  • Levomilnacipran (Fetzima)
  • Venlafaxine (Effexor XR)

Add-on drugs or other therapies. About 30% to 50% of people with depression might still have symptoms when they're on an antidepressant. If that happens to you, Sanacora says your doctor might give you another kind of treatment at the same time. That may include things like:

  • Atypical antidepressants
  • Atypical antipsychotics
  • Ketamine nasal spray (an anesthetic)

Another option is brain stimulation techniques, including:

  • Electroconvulsive therapy (ECT)
  • Transcranial magnetic stimulation (TMS)
  • Vagus nerve stimulation (VNS)

Cyclic antidepressants. These are the oldest antidepressants. They come with a lot more side effects than newer drugs. Your doctor might suggest them if other treatments don’t work. 

Questions to Ask Your Doctor

Danesh Alam, MD, a psychiatry specialist at Northwestern Medicine, says "depression is one of the most complicated illnesses we have in medicine." And to get the best treatment, it’s important to get on the same page as your doctor.

Continued

"You have to reach a target dose and identify your target symptoms," he says. "A lot of times, these details aren’t looked at. Then it becomes a mismatch of expectations. That’s what I’d call a therapeutic failure, not a medication failure."

Here are some questions about antidepressants that you might want to bring up:

  • When should I see results?
  • Will I feel worse before I feel better?
  • How often should I follow up?
  • What are common side effects? How long do they last?
  • How do I know if side effects are serious?
  • What happens if the drug stops working?
  • How long should I stay on an antidepressant?
  • How do I know if I need to change the dose?
  • What are nondrug treatments for depression?
  • What is the plan for stopping the drug?

 

Don’t Give Up Too Early

It’s normal to want to feel better fast. But it takes time for antidepressants to work. Experts aren’t exactly sure why. One theory is that it can take days or weeks for these drugs to change the chemical pathways that lead to depression. We need more research to know for sure.

Continued

While everyone is different, it can take an average of 4-6 weeks to see big improvements.

"But to truly say that a medication doesn’t work, you have to give it 8 weeks," Alam says.

And don’t give up if your first antidepressant isn’t a good fit. Studies show your chances of success go up if you try more than one approach.

"The important message is that medication and treatment for depression is effective," Alam says. "But you have to stay engaged with treatment."

WebMD Feature

Sources

SOURCES:

Gerard Sanacora, PhD, MD, director, Yale Depression Research Program; George D. and Esther S. Gross professor of psychiatry, Yale School of Medicine; co-director, Yale New Haven Hospital Interventional Psychiatry Service.

Danesh Alam, MD, psychiatry specialist, Northwestern Medicine.

The Lancet: "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis."

Lancet Psychiatry: "How do antidepressants work? New Perspectives for refining future treatment approaches."

FamilyDoctor.org: "Types of antidepressants."

Mayo Clinic: "Serotonin and norepinephrine reuptake inhibitors (SNRIs)."

International Journal of Neuropsychopharmacology: "Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning."

UpToDate: "Unipoloar depression in adults: Treatment with second-generation antipsychotics."

Pharmacy and Therapeutics: "Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant."

Journal of Psychiatry & Neuroscience: "Adult neuroplasticity: A new ‘cure’ for major depression?

National Institute of Mental Health: "Questions and Answers about the NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study -- All Medication Levels."

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