Medically reviewed by Kristin Hall, FNP
Written by Our Editorial Team
Last updated 11/10/2020
Selective serotonin reuptake inhibitors, commonly referred to as SSRIs, are some of the most widely prescribed medications in the United States.
SSRIs are primarily to treat depression. They work by increasing the level of serotonin in your brain and body. Serotonin plays an essential role in regulating your mood, and people with low levels of serotonin are often affected by depression.
For most people with depression or anxiety, SSRIs are a safe, effective form of treatment that produce real, noticeable results. However, not everyone with depression or anxiety gets good results from SSRIs.
For some people, SSRIs can cause side effects. For others, using an SSRI might not produce any significant improvement in their depression or anxiety symptoms.
Luckily, alternatives to SSRIs are available. From other antidepressants to psychotherapy and lifestyle changes, there are numerous SSRI alternatives that can allow you to treat depression or anxiety without using medications of this type.
Below, we’ve provided a complete list of SSRI alternatives for people affected by depression or anxiety disorders. We’ve also explained how each option works, its advantages, disadvantages, potential side effects and more.
Before getting into SSRI alternatives, it’s important to explain why you may not want to use an SSRI if you’ve been diagnosed with a form of depression or anxiety.
SSRIs are antidepressants. Although most people associate SSRIs with depression, they can actually be used to treat several other conditions, including several common anxiety and mood disorders.
Although most SSRIs are generally safe and effective, they’re not always the best option if you have depression, anxiety or a mood disorder. Common downsides of SSRIs include:
Side effects. Although SSRIs are generally less likely to cause side effects than older antidepressants, side effects are still quite a common experience for some people who use SSRIs to treat depression or anxiety.
As we’ve covered in our full guide to SSRIs, common SSRI side effects include nausea, agitation, anxiety and dizziness. Although these are often temporary, it’s possible for some SSRI side effects to persist or become overly severe.
The risk of side effects can vary significantly from one SSRI to another. However, if you are prone to side effects from SSRIs, it’s completely understandable that you may want to use a different type of medication.
Drug interactions. SSRIs can interact with other medications. While some interactions aren’t serious, others can be life-threatening. For example, SSRIs can cause serotonin syndrome — a dangerous reaction — when used with other serotonin-affecting drugs.
Medications that can interact with SSRIs include other antidepressants, blood thinning medications, nonsteroidal anti-inflammatory drugs (NSAIDs) and others.
Withdrawal symptoms. Like many other medications, SSRIs and other antidepressants may cause withdrawal symptoms if they’re stopped abruptly. These are often referred to as antidepressant discontinuation syndrome.
Suicide risk. Although the potential suicide risk of antidepressants subject is subject to some scientific controversy, SSRIs and other antidepressants come with a warning from the FDA noting of their risk of causing suicidal thoughts or behavior in young people.
This risk is present in people aged 24 and under. It’s worth noting that this warning can be found on the packaging for all antidepressants, not only SSRIs, meaning that using one antidepressant over another may not affect the risk of suicidal actions.
If you’re at risk of any of the issues listed above, using an SSRI may not be the most effective option for you. However, if you’re currently prescribed an SSRI, you should always check with your healthcare provider before making any changes to your current medication usage.
Finally, some people simply don’t find SSRIs effective. Approximately one third of people who use antidepressants notice something known as “breakthrough depression” — a return of their depression symptoms after a period of their medication working normally.
Others simply don’t notice an improvement at all. In fact, according to data from Northwestern University, about half of all people who use antidepressants don’t experience noticeable relief from depression.
SSRIs aren’t the only option for treating depression and anxiety disorders. Other options may include psychotherapy, medications other than SSRIs and changes to your lifestyle and habits that help to minimize or manage your symptoms.
If you have depression, other, non-SSRI antidepressants may be able to provide similar relief from your depression symptoms and help you work towards a long-term recovery. Non-SSRI antidepressants include:
Serotonin–norepinephrine reuptake inhibitors (SNRIs). These medications function similarly to SSRIs, but also increase the level of the neurotransmitter norepinephrine in your brain. Norepinephrine is believed to affect your body’s response to stress.
Common SNRIs include venlafaxine (sold as Effexor®), duloxetine (Cymbalta®) and desvenlafaxine (Pristiq®).
Bupropion. Sold under the brand name Wellbutrin®, this is an atypical antidepressant that works by affecting the neurotransmitters norepinephrine and dopamine.
Research has shown that bupropion is less likely to cause sexual side effects than other medications used to treat depression. As such, it’s often used as an SSRI alternative, or as a secondary medication in combination with an SSRI or SNRI.
Tricyclic antidepressants (TCAs). These are an older class of antidepressants that aren’t used as frequently today. As with other antidepressants, they work by affecting the neurotransmitters that contribute to depression.
TCAs are designed to treat depression, but can cause more side effects and interactions than newer medications. Despite their side effect risk, TCAs are still prescribed to treat depression when other, newer medications haven’t worked effectively.
Monoamine oxidase inhibitors (MAOIs). Another older class of antidepressants, these work by targeting the enzyme monoamine oxidase, which is responsible for controlling a variety of neurotransmitters in the brain.
Like TCAs, MAOIS generally aren’t widely used today due to their side effects. Not only can they interact with other medications, but they can also cause dangerous interactions if they’re used with certain foods, such as cheeses and cured meats.
Despite this, MAOIs may be prescribed as an alternative antidepressant in some cases if newer medications aren’t effective.
If you’re prescribed an SSRI for an anxiety disorder rather than depression, you may be able to switch to a different type of anti-anxiety medication. Options include:
Benzodiazepines. These medications are often used to treat anxiety in the short term, as they work quickly and provide relief from anxiety symptoms in as little as 30 minutes to one hour.
However, they’re not recommended for long-term use, as they can cause dependence, become less effective over time and lead to withdrawal symptoms.
Buspirone. This is a modern anti-anxiety medication. It’s less likely to cause side effects than other medications and has no associated risk of causing dependence or withdrawal symptoms if treatment is stopped abruptly.
Buspirone is often prescribed as a second-line medication for people who don’t respond to SSRIs or experience side effects when using SSRIs to treat anxiety.
Depression, anxiety and other conditions for which SSRIs are commonly prescribed are often treated using psychotherapy.
One of the most effective, well-estimated forms of therapy for treating depression is cognitive behavioral therapy, or CBT. It involves identifying and understanding the thought processes and behavior that can contribute to depression and anxiety symptoms.
One advantage of cognitive behavioral therapy is that it gives you control over your progress towards recovery. It usually takes 12 week to 16 weeks of therapy to see significant improvements from this type of therapy.
Depending on your disorder, you may benefit from other forms of therapy. Common forms of therapy used to treat depression, anxiety and other conditions often treated using SSRIs can include interpersonal therapy (IPT) and dialectical behavior therapy (DBT).
Sometimes, therapy alone may be enough to provide relief from depression and/or anxiety. In some cases, you may need to take one of the medications listed above in combination with a form of therapy to treat your symptoms and work towards recovery.
Learn about an alternative type of therapy here: EFT Tapping: What Is It and Does It Work for Anxiety?
Some natural treatments, including herbal products and supplements, may offer some benefits for people with depression, anxiety and other mood disorders that are commonly treated using SSRIs.
However, these products should not be relied on as proven treatments for depression, anxiety or other mood disorders. If you’re currently prescribed an SSRI or other medication, don’t stop using it without first talking to your healthcare provider.
Common “natural antidepressants” include St. John’s wort — a herbal supplement found in teas, tablets and other products. While there’s some evidence that it may provide benefits for treating mild to moderate depression, research has found that it isn’t consistently effective.
If you use St. John’s wort to treat mild to moderate depression, make sure not to use it with any other antidepressants. Combining St John’s wort with some antidepressants can potentially lead to serotonin syndrome — a dangerous, life-threatening reaction.
In general, there’s little evidence that these treatments are effective, with few or no large-scale, high quality studies into their effects.
While most people associate treating depression with therapy and medication, making positive changes to your lifestyle and habits can have a surprisingly large impact.
Like natural treatments, lifestyle changes shouldn’t be viewed as perfect alternatives to antidepressants. However, they can complement other treatments for depression and anxiety, helping you to control your symptoms and make better progress towards recovery.
If you’re currently prescribed an SSRI, don’t stop taking it just to make changes to your habits and lifestyle. Instead, talk to your healthcare provider about how certain lifestyle changes and new habits may fit into your treatment.
Lifestyle changes to consider include exercising regularly, eating a balanced diet, making sure you get enough sleep, taking steps to reduce stress in your life and spending time with friends, family and other loved ones.
While these may seem simple, they can make a big difference, especially when combined with therapy and medication.
SSRIs are commonly prescribed to treat depression and anxiety disorders. They generally work well, but they’re not always effective for everyone. For some people, they can cause side effects that make alternative methods of treatment worth considering.
If you have depression and don’t want to use an SSRI, you may benefit from a different type of antidepressant, such as an SNRI, TCA, MAOI or bupropion. For anxiety, you may benefit from an anti-anxiety medication, such as buspirone.
Stopping SSRIs suddenly can cause withdrawal symptoms. To keep yourself safe and prevent your symptoms from worsening, make sure to talk to your healthcare provider before you make any changes to the way you use your medication.
For expert help, you can receive an evaluation for depression treatment online to learn more about your treatment options.
In use since the late 1980s, SSRIs are some of the most common medications for depression and anxiety disorders. Our complete guide to SSRIs goes into greater detail about how SSRIs work, common SSRI medications, potential side effects and more.