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Don’t feel like your antidepressants are working effectively? Experiencing annoying, persistent side effects? You’re not alone. The truth is, antidepressants don’t always work — at least, not all antidepressants work for everyone.
In fact, it’s not uncommon for people to try multiple antidepressants before finding one that works best for them.
If you’re prescribed antidepressant medication and don’t feel like it’s working as effectively as expected, or if you have unpleasant or persistent side effects, consider talking to your healthcare provider about switching to a new type of medication.
There’s often a degree of trial and error involved in finding the right antidepressant. For lots of folks, switching medications several times is a critical step in identifying the specific antidepressant that best suits their symptoms and needs.
Below, we’ll list common reasons for switching antidepressants, as well as the medications you may be prescribed by your healthcare provider. We’ll also go over key information you should be aware of, from side effects to methods of switching.
Needing to switch your antidepressant medication can occur for many reasons, including what it’s treating. You might be on one of these medications for depression, anxiety or various other mood, mental health or compulsive disorders.
Regardless of what it’s treating, there are several reasons why you may want to switch antidepressants, from side effects to a lack of effectiveness. Some of the most common reasons to change antidepressants include:
Side effects. Many antidepressants can cause side effects, including nausea, digestive issues, headaches and difficulty sleeping.
Though many side effects are common across antidepressants, the likelihood and severity of certain side effects can vary from one medication to another. If you experience side effects from one antidepressant, your healthcare provider may recommend switching to another.
Lack of effectiveness. While antidepressants are largely effective at treating major depressive disorder (MDD), not all people experience improvements after they start taking an antidepressant. It’s a good idea to go into treatment prepared to try a few different medications. That way, you'll be less likely to give up if the first one isn’t quite right for you.
Sexual side effects. Some antidepressants, including commonly prescribed ones from the class known as SSRIs (selective serotonin reuptake inhibitors), can cause sexual side effects such as erectile dysfunction, decreased sex drive and difficulty reaching orgasm (anorgasmia). For some, switching to another type of antidepressant can reduce the severity of these sexual side effects.
Weight gain. Some side effects, such as weight gain, occur more frequently with certain types of antidepressant medication. Switching to a new type of antidepressant may help reverse any weight gain you’ve experienced during treatment.
Research shows that approximately one-third of people with depression have treatment-resistant depression (TRD). With TRD, depression doesn’t always improve through standard treatments, like antidepressants or psychotherapy.
If you have treatment-resistant depression, or your depression doesn’t respond to the antidepressant you’re currently taking, you may need to try several antidepressants before finding one that works.
In some cases, such as when your current medication isn’t effectively treating your depression, your healthcare provider may suggest changing to a different medication within the same class of antidepressants, such as from one SSRI to another.
If you think switching to a new antidepressant could be a good idea, talk to your healthcare provider. When switching antidepressants, your healthcare provider may recommend switching directly, cross-tapering or tapering down your dosage before you start using your new medication.
Depending on the type of antidepressant you’re currently using and the medication you switch to, you’ll need to follow one of four techniques to switch medications:
Direct switch. If it’s safe to switch from one antidepressant to another immediately, you may be able to stop taking your current antidepressant and immediately start using the new one the very next day. Switching directly is usually only a safe option for switching between certain SSRIs and SNRIs with short half-lives, as these medications are less likely to cause drug interactions or unwanted side effects. You’ll also be able to make a direct switch if you’re currently taking the lowest dose of your medication.
Cross-tapering. To cross-taper, you’ll need to gradually reduce the dosage of your old antidepressant while gradually increasing the dosage of your new medication at the same time. This technique may be used if your medication puts you at risk for withdrawal symptoms, which may occur when some antidepressants are stopped without a gradual taper.
Taper and moderate switch. One of the safer techniques simply reduces your current dosage to a complete stop, then waits for it to clear your body before starting the new antidepressant. You may need to use this technique if you’re using an antidepressant that can interact with the other medication.
Taper and conservative switch with a medication-free washout period. Since some tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) can cause harmful interactions if used within 14 days of starting treatment with other antidepressants, you may need to include what’s called a washout period. For medications with a shorter half-life, you might only have to wait two to four days before you begin using the new antidepressant at a low dose.
There’s no one-size-fits-all process for switching from one antidepressant to another. To avoid drug interactions, your healthcare provider will tell you which process to use and how to switch from one antidepressant to another safely based on your medications and overall health.
The strategy your healthcare provider chooses depends on the following factors:
Which drugs you currently and how high the dose is
The severity of your symptoms
Your concerns over symptoms
If you’ve been using your current antidepressant for several months and haven’t experienced improvements or have unpleasant side effects, your healthcare provider may recommend one of the following types of antidepressants:
Selective serotonin reuptake inhibitors (SSRIs). SSRIs are modern antidepressants often used as a first-line treatment for major depressive disorder. Common SSRIs include Prozac® (fluoxetine), Zoloft® (sertraline) and Lexapro® (escitalopram). Effectiveness and side effect rates can vary between SSRIs. As such, your healthcare provider may suggest switching to a different SSRI, even if you currently use this type of antidepressant. See our guide to switching from Lexapro to Zoloft to learn more.
Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs are another class of modern antidepressants. Common SNRIs include Cymbalta® (duloxetine), Effexor XR® (venlafaxine) and Pristiq® (desvenlafaxine).
Tricyclic antidepressants (TCAs). Tricyclic antidepressants are older antidepressants that, due to their side effect profiles, typically aren’t prescribed as first-line depression treatments today. Despite their side effects, some tricyclic antidepressants may be effective for improving depression symptoms when other, newer medications aren’t effective.
Atypical antidepressants. Atypical antidepressants like Wellbutrin® (bupropion) target neurotransmitters other than serotonin and are prescribed when SSRIs and other antidepressants aren’t fully effective.
Monoamine oxidase inhibitors (MAOIs). MAOIs are an older class of antidepressants, primarily used in the 20th century. Because of their side effects and interaction risk, most MAOIs have been replaced by newer antidepressants over the years. In some cases, MAOIs may be prescribed to treat depression when newer medications aren’t effective.
It’s important to closely follow the instructions provided by your healthcare provider, as switching medications incorrectly or too quickly may increase your risk of experiencing drug interactions and adverse effects.
Common side effects of antidepressant switching or discontinuation include:
Returning symptoms of depression
Electric shock sensations
Delirium and psychosis
Don’t ever adjust your dosage or stop taking your antidepressant without talking to your healthcare provider or prescriber. Changing your dosage or abruptly stopping your medication could cause you to experience antidepressant withdrawal symptoms like those electric shocks — also known as “brain zaps.”
Before you get overwhelmed by the details, let’s get our priorities straight and our message clear: You can switch your antidepressant treatment safely, but you’ll have to follow a smart, professionally designed switching strategy.
Switching antidepressants isn’t uncommon. In fact, many people prescribed antidepressants try several medications before finding the one that works best for them. But working with your prescriber is the best way to avoid discontinuation symptoms, serotonin syndrome and other issues.
If you’re prescribed an antidepressant and don’t feel like it’s working, it’s essential that you talk to your healthcare provider before making any changes.
That said, there are some key takeaways you should keep in mind before, after and during those conversations. Whether you eventually switch medications or not, remember this:
It’s common to switch antidepressants once, twice or possibly even a third time if your healthcare provider recommends that course of action.
Changing to a new medication may help you to recover from depression more effectively — or simply avoid unpleasant or persistent side effects that occurred with your previous antidepressant.
Based on your symptoms, the medication you’re currently using, and your overall health, your healthcare provider will work with you to find an antidepressant that’s safe to switch to, effective and suitable for your needs.
If you just recently started taking antidepressants and haven’t noticed any improvement in your mood or general well-being, don’t panic. It typically takes several weeks for most antidepressants to start working and, sometimes, months before they reach full effectiveness.
If your antidepressant isn’t working after several weeks or is causing side effects, you might not need to change to a new medication. Your healthcare provider may suggest a different dosage or frequency of your current medication.
Don’t stop your current antidepressant or adjust your dosage without professional guidance. This could cause you to experience antidepressant withdrawal symptoms or a relapse of your depression symptoms.
Want to really dig into the minutiae of these medications? Like, seriously trying to nerd out? Check out our full antidepressant list for a comprehensive guide to the most popular depression medications on the market today.
And if you’re considering a switch right now, you may want to look at our medication-specific guides. We’ve covered the nitty-gritty of switching between common antidepressants in our blog, including:
Dr. Daniel Z. Lieberman is the senior vice president of mental health at Hims & Hers and of psychiatry and behavioral sciences at George Washington University. Prior to joining Hims & Hers, Dr. Lieberman spent over 25 years as a full time academic, receiving multiple awards for teaching and research. While at George Washington, he served as the chairman of the university’s Institutional Review Board and the vice chair of the Department of Psychiatry and Behavioral Sciences.
Dr. Lieberman’s has focused on , , , and to increase access to scientifically-proven treatments. He served as the principal investigator at George Washington University for dozens of FDA trials of new medications and developed online programs to help people with , , and . In recognition of his contributions to the field of psychiatry, in 2015, Dr. Lieberman was designated a distinguished fellow of the American Psychiatric Association. He is board certified in psychiatry and addiction psychiatry by the American Board of Psychiatry and Neurology.
As an expert in mental health, Dr. Lieberman has provided insight on psychiatric topics for the U.S. Department of Health and Human Services, U.S. Department of Commerce, and Office of Drug & Alcohol Policy.
Dr. Lieberman studied the Great Books at St. John’s College and attended medical school at New York University, where he also completed his psychiatry residency. He is the coauthor of the international bestseller , which has been translated into more than 20 languages and was selected as one of the “Must-Read Brain Books of 2018” by Forbes. He is also the author of . He has been on and to discuss the role of the in human behavior, , and .
1992: M.D., New York University School of Medicine
1985: B.A., St. John’s College, Annapolis, Maryland
2022–Present: Clinical Professor, George Washington University Department of Psychiatry and Behavioral Sciences
2013–2022: Vice Chair for Clinical Affairs, George Washington University Department of Psychiatry and Behavioral Sciences
2010–2022: Professor, George Washington University Department of Psychiatry and Behavioral Sciences
2008–2017: Chairman, George Washington University Institutional Review Board
2022: Distinguished Life Fellow, American Psychiatric Association
2008–2020: Washingtonian Top Doctor award
2005: Caron Foundation Research Award
Lieberman, D. Z., Cioletti, A., Massey, S. H., Collantes, R. S., & Moore, B. B. (2014). Treatment preferences among problem drinkers in primary care. International journal of psychiatry in medicine, 47(3), 231–240. https://journals.sagepub.com/doi/10.2190/PM.47.3.d?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Lieberman, D. Z., Swayze, S., & Goodwin, F. K. (2011). An automated Internet application to help patients with bipolar disorder track social rhythm stabilization. Psychiatric services (Washington, D.C.), 62(11), 1267–1269. https://ps.psychiatryonline.org/doi/10.1176/ps.62.11.pss6211_1267?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Lieberman, D. Z., Massey, S. H., & Goodwin, F. K. (2010). The role of gender in single vs married individuals with bipolar disorder. Comprehensive psychiatry, 51(4), 380–385. https://www.sciencedirect.com/science/article/abs/pii/S0010440X0900128X?via%3Dihub
Lieberman, D. Z., Kolodner, G., Massey, S. H., & Williams, K. P. (2009). Antidepressant-induced mania with concomitant mood stabilizer in patients with comorbid substance abuse and bipolar disorder. Journal of addictive diseases, 28(4), 348–355. https://pubmed.ncbi.nlm.nih.gov/20155604
Lieberman, D. Z., Montgomery, S. A., Tourian, K. A., Brisard, C., Rosas, G., Padmanabhan, K., Germain, J. M., & Pitrosky, B. (2008). A pooled analysis of two placebo-controlled trials of desvenlafaxine in major depressive disorder. International clinical psychopharmacology, 23(4), 188–197. https://journals.lww.com/intclinpsychopharm/abstract/2008/07000/a_pooled_analysis_of_two_placebo_controlled_trials.2.aspx
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