Several alternatives exist for SSRIs. Alternatives include selective-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and benzodiazepines. Other alternatives include Buspar, Wellbutrin, serotonin modulators, antipsychotics, and ketamine. Alternatives are usually just as effective, but their downside is that they can have more side effects, and some are potentially dangerous.
If you’re considering non-SSRI antidepressants, online psychiatry platforms such as Talkiatry and Brightside can connect you with a provider quickly. These platforms can provide an assessment and may offer you a prescription if they determine a medication may help your symptoms.
What Are SSRIs?
Selective serotonin reuptake inhibitors (SSRIs)* are a drug class commonly used to treat anxiety, depression, and other psychiatric conditions.1 They act by binding to receptors in the brain to prevent the breakdown of serotonin, a naturally occurring neurotransmitter. Antidepressants make you feel like your mood is more uplifted. Your appetite may also return, as well as feeling improvements with sleep and memory. Usually, it takes around 2 weeks for antidepressants to work, and 4-8 weeks to feel their full effects.
*SSRIs have a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting these medications.
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When to Consider Non-SSRI Antidepressants
An SSRI is a first-line treatment for depression and anxiety treatment, but may not be suitable for everyone or all situations. In general, you should not take an SSRI if you have seizures, are on blood thinners, or are at risk for low sodium levels. You should also not take SSRIs if you drink alcohol or take medications or substances that increase serotonin.
Reasons someone may consider an SSRI alternative include:
Antidepressant Withdrawal
Antidepressant withdrawal is the negative symptoms experienced if you suddenly stop or drastically decrease your dose of an SSRI that you have been taking for several months. It is common to experience withdrawal, and symptoms can be severe. Withdrawal symptoms include nausea, irritability or agitation, flu-like symptoms (body aches, sweating, lethargy), headache, and dizziness.2
Side Effects
Common side effects of SSRIs include headache, dizziness, nausea or vomiting, female and male sexual issues, rash, trouble sleeping, extreme tiredness, and increased or decreased appetite.2,3
Lack of Effectiveness
You may develop a tolerance to your medication over time or find it is no longer helpful. Over time, the brain’s receptors to a drug can increase to compensate for the drug intake and result in tolerance. You may also have taken on more stress in your life from being on medication, which can make the drug appear ineffective. Also, a medication may not work at all for some people.
10 Alternatives To SSRIs
There are many alternatives to SSRI medications you can explore. Factors you should consider before meeting with their doctor to discuss an alternative include your symptoms, so they know which side effects to avoid, and if you if you have a history of addictive behavior or substance misuse.
Here are 9 alternatives to SSRIs:
1. Selective-norepinephrine Reuptake Inhibitors (SNRIs)
An alternative option for anxiety and depression includes Selective-norepinephrine reuptake inhibitors (SNRIs), which work similarly to SSRIs but also increase norepinephrine levels in the brain. In general, SNRIs compare to SSRIs similarly in effectiveness and tolerability. You should not take SNRIs if you have an increased risk of bleeding, a history of suicidal thoughts or ideation, low sodium levels, or are pregnant.4,5
Commonly prescribed SNRI medications include:
*This medication has a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting this medication.
Common side effects of SNRIs include:4,5
- Weight and appetite changes
- Headache
- Trouble sleeping or drowsiness
- Dizziness
- Dry mouth
- Male and female sexual issues
- Nausea
2. Tricyclic Antidepressants (TCAs)
Another class of medications sometimes used for anxiety and depression includes TCAs. They act on several receptors, including serotonin, norepinephrine, histamine, and alpha 2 in the brain.6 These receptors improve mood and lead to relaxation. Since they act on multiple receptors, they often have a lot of side effects limiting their use.
However, if you have tried other antidepressants, your doctor may try a TCA. They may also choose a TCA if you also have headaches or insomnia, as some of them have these additional approved uses. You should not take TCAs if you are recovering from a heart attack or you have a history of suicidal thoughts or bipolar disorder.6,7
Commonly prescribed TCA antidepressants include:
- Elavil (amitriptyline)*
- Asendin (amoxapine)*
- Norpramin (desipramine)*
- Selenor (doxepin)*
- Tofranil (imipramine)*
- Pamelor (nortriptyline)*
*This medication has a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting this medication.
Common side effects of TCA antidepressants include:6,7
- Headache
- Constipation
- Dizziness
- Dry mouth
- Blurred vision
- Confusion
- Urinary retention
- Fast heart rate
- Low blood pressure upon standing or sitting up
- Sedation
- Increased appetite or weight gain
3. Monoamine Oxidase Inhibitors (MAOIs)
Another drug class that acts on serotonin includes monoamine oxidase inhibitors (MAOIs). They work in serotonin indirectly by acting as a transporter for tyrosine, the protein that makes up serotonin.8 These have dangerous drug interactions and side effects, so they are not commonly used since so many other options exist. This drug should not be mixed with other antidepressants because serotonin syndrome or a life-threatening neurological disorder can occur.
However, they may be used if you’ve tried all of the above options. You should not take MAOIs if you have high blood pressure, a history of suicidal thoughts or ideation, pheochromocytoma (a type of tumor that can increase blood pressure), liver or kidney disease, or an allergy to an MAOI.8,9
Commonly prescribed MAOIs include:
- Marplan (isocarboxazid)*
- Nardil (phenelzine)*
- Emsam (selegiline)*
- Parnate (tranylcypromine)*
*This medication has a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting this medication.
Common side effects of MAOIs include:8,9
- Nausea
- Dry mouth
- Dizziness
- Headache
- Drowsiness
- Weight gain
- Sexual issues
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*Includes copayment, deductible, coinsurance, and $0 Visits. Excludes no shows. **On average. Actual appointment times vary by state and individual patient.
4. Benzodiazepines
Benzodiazepines act on gamma-aminobutyric acid (GABA) receptors to increase GABA in the brain10 and are approved for anxiety. They are chosen over other medications when anxiety is severe and accompanied by panic, posttraumatic stress disorder, or trouble sleeping. Benzodiazepines are less commonly used, though, because they have serious slide effects and drug interactions and can result in benzodiazepine withdrawal when stopped.
Commonly prescribed benzodiazepine medications include:
- Xanax (alprazolam)**
- Klonipin (clonazepam)**
- Valium (diazepam)**
- Ativan (lorazepam)**
- Restoril (temazepam)**
**This medication has black box warnings, the most serious kind of warnings from the FDA for abuse or misuse, risk of physical dependence and risk of serious side effects, including death, when combined with an opioid.
Common side effects of benzodiazepines include:10,11
- Extreme tiredness
- Light-headedness
- Dry mouth or increased salivation
- Dizziness
- Low blood pressure
- Allergic reaction
5. Buspar (Buspirone)
Buspirone is an anti-anxiety medication that has high activity for serotonin receptors and moderate activity for dopamine receptors.12 Buspar, the brand name version of this medication, was discontinued several years ago, but the generic version (buspirone) is widely available.
Buspirone does not have a chance of addiction and is considered safer with less serious side effects. The disadvantage of buspirone includes that it is only approved for generalized anxiety disorder. Buspirone is also used off-label for depression. You should not take buspirone if you have an allergy to it or are 5 years or younger.
Common side effects of buspirone include:12
- Dizziness
- Nausea
- Headache
- Nervousness
- Light-headedness
- Excitement
6. Wellbutrin (Bupropion)
Wellbutrin affects serotonin and dopamine levels in the brain.13 It is also considered safe and does not have a potential for addiction. Wellbutrin is used for depression and has an off-label use for attention deficit hyperactive disorder. You should not take Wellbutrin if you have a history of suicidal thoughts or ideation, seizures, bulimia, or anorexia or are breastfeeding.
Common side effects of Wellbutrin include:13
- Abdominal pain
- Agitation or anxiety
- Dizziness
- Dry mouth
- Trouble sleeping
- Muscle pain
- Nausea
- Palpitations
- Pharyngitis
- Sweating
- Ear ringing
- Urinary frequency
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7. Serotonin Modulators
Serotonin modulators work by increasing the amount of serotonin in the brain.14 They are used when an inadequate response or documented intolerance due to severe adverse reaction or contraindication to at least two preferred agents. These may be chosen after many of the above drugs are tried. You should not take these medications if you have a history of suicidal ideation or behavior, or seizures.
Commonly prescribed serotonin modulators include:
- Nefazodone*
- Viibryd (vilazodone)*
- Britellix and Trintellix (vortioxetine)*
*This medication has a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting this medication.
Common side effects of serotonin modulators include:14,15
- Light-headedness
- Extreme tiredness
- Constipation or diarrhea
- Trouble sleeping
- Dizziness
- Dry mouth
- Blurred vision
- Confusion
8. Antipsychotics
Antipsychotics are a drug class approved for major depressive disorder and depression from bipolar disorder.16 They work by increasing serotonin and dopamine. Antipsychotics may be chosen after many of the medications above have been tried, as these often have many side effects. You should not take antipsychotics if you have a history of suicidal ideation or behavior, are pregnant or breastfeeding, or are 12 years or younger.
Commonly prescribed antipsychotics include:
- Seroquel (quetiapine)
- Zyprexa (olanzapine)
- Risperdal (risperidone)
- Geodon (ziprasidone)
*This medication has a black box warning, the most serious kind of warning from the FDA for a risk of suicidal thoughts and behaviors in certain people. You should talk with your doctor about these risks before starting this medication.
Common side effects of antipsychotics include:16,17
- Drowsiness or extreme fatigue
- Weight gain
- Dizziness
- Constipation
- Dry mouth
- Indigestion
9. Trazodone
Trazodone is another medication used for depression and off-label for anxiety and sleep disorders. Its overall effect works by increasing serotonin as an SSRI. Trazodone may be chosen for its many uses after trying many SSRIs. You should not take trazodone if you have a history of suicidal ideation or behavior or are pregnant or breastfeeding.
Common side effects of trazodone include:18
- Extreme tiredness
- Swelling
- Blurry vision
- High blood pressure
- Weight changes
10. Ketamine
Ketamine, or esketamine, is used for depression after several agents for an adequate amount of time without response.19It has the advantages of coming as an inhalation for easy administration, working almost immediately. Ketamine works by inhibiting N-methyl-D-aspartate (NMDA) receptors. This means that Ketamine slows or blocks the stimulating signals to the NDMA receptors, making them less active.20
You should not take ketamine if a severe increase in blood pressure is dangerous or if you have an allergy to ketamine, are pregnant or breastfeeding, are below the age of 16, or are older than 65 years.
Common side effects of ketamine include:20
- Elevated blood pressure or heart rate
- Low blood pressure or heart rate
- Irregular heart rate
- Double vision
- Rapid, uncontrolled eye movement back and forth
- Elevated eye pressure
- Anorexia, nausea, or vomiting
Online Psychiatry and Medication Management Covered by Insurance
Talkiatry can match you with a real psychiatrist who takes your insurance and is seeing new patients. They’re in-network with major insurers and offer medication management. Get started with a short online assessment
Other Treatments for Depression & Anxiety
Non-medicinal approaches to treating depression and anxiety include therapy, lifestyle changes, and natural remedies. Lifestyle changes include physical exercise, a healthy diet and sleep routine, pursuing your hobbies, and hanging out with friends regularly. Natural remedies include different supplements. Non-medical approaches are important because they help supplement your mental health and cause the release of your brain’s natural mood-enhancing chemicals.
Psychotherapy
Psychotherapy can sometimes be as beneficial as an alternative to SSRI medications. It can help you overcome problems and increase happiness. Combining medication with psychotherapy is often recommended to get the benefits of both. Medication helps change the brain chemistry, while therapy helps you learn how to prevent symptoms or behaviors that are causing you emotional distress. An example of psychotherapy includes emotional freedom technique (EFT) tapping to distract yourself.
However, sometimes psychotherapy is considered over medication for depression and anxiety due to drug interactions or side effects, if you are uncomfortable taking medication, or each medicine gives you intolerable side effects. There are several options for anxiety therapy and depression therapy.
Lifestyle Changes
Lifestyle changes may be helpful when dealing with depression and anxiety. They can increase your physical health and social health while building stress tolerance. Physical exercise releases feel-good hormones and is recommended to help reduce symptoms. Meditation and therapy can help support your emotional health, while having a healthy sleep routine and diet can help support thought processing.
Lifestyle changes that may help reduce symptoms of depression and anxiety include:
- Staying physically active: Mental health benefits of exercise include relief from anxiety, stress, and depression. It is recommended to do strenuous exercise for 30 minutes 4-5 days a week for several weeks.
- Maintaining a healthy sleep routine: A sleep routine also helps support your mental health by helping regulate your emotions, behaviors, and body.
- Practicing meditation: Meditation for anxiety can help by teaching you to be present. It also has numerous physical benefits.
- Stay hydrated and well-nourished: Drinking plenty of water and eating nutritious food supports your mental health by giving your body the nutrients it needs.
- Pursue hobbies and time with friends: Enjoying your hobbies or friends daily is very beneficial to mental health by giving you goals and feelings of accomplishment and helping with stress relief.
Natural Remedies
If you decide you would like to try other anxiety options first, there are alternative natural remedies for anxiety that can be found in drugstores. Certain supplements may help ease anxiety, like matcha and L-theanine.21,22 Other supplements that can help anxiety include magnesium and omega-3 fatty acids.23,24 High doses of Vitamin B6 have also been shown to decrease anxiety.25
Supplements that can help ease depression symptoms include St John’s Wort***, probiotics, and folate.26,27,28 Also, adenosylmethionine (SAM-e) and saffron are used to help anxiety and depression.29,30 Before taking supplements, ask your doctor if certain ones you are considering will interact with your medications. In addition, supplements can have side effects and are not suited for everyone.
***Dietary supplements (including vitamins, supplements, herbs, and natural medicines) are not regulated the same way as medications by the FDA. Before being sold to the public, these products do not have the same clinical trials to determine their safety and efficacy. You should consult your doctor or pharmacist before starting any new dietary supplement.
Questions to Ask Before Considering Non-SSRI Antidepressants
You should ask your doctor questions before considering non-SSRI medications or alternative treatments. Questions include how long it takes for the medications to work, what side effects you should expect, and which side effects you should expect to go away over time. You should also ask if supplements for anxiety or depression are safe to take with your medication.
Before seeking an alternative to your SSRI medication, consider asking your doctor/psychiatrist the following questions:
- Why should I consider other medications for my depression?
- Are there certain alternatives to SSRIs that I should avoid?
- What are some online therapy options with my insurance that I can pair with my antidepressant treatment?
- How long does it take for alternatives to SSRIs to work?
- Which side effects should I expect to go away over time?
- Which side effects will go away over time?
- Are supplements for anxiety or depression safe to take with your medication?
- What side effects from supplements are most common?
In My Experience
In my experience, most patients are able to find a medication for anxiety and depression that works and is tolerable. When switching medications, you should not experience withdrawal symptoms. If you find you would no longer like to keep trying medications, there are lots of alternative and natural solutions. However, it also takes time to see results.
Additional Resources
To help our readers take the next step in their mental health journey, Choosing Therapy has partnered with leaders in mental health and wellness. Choosing Therapy is compensated for marketing by the companies included below.
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Best Online Psychiatry Services
Online psychiatry, sometimes called telepsychiatry, platforms offer medication management by phone, video, or secure messaging for a variety of mental health conditions. In some cases, online psychiatry may be more affordable than seeing an in-person provider. Mental health treatment has expanded to include many online psychiatry and therapy services. With so many choices, it can feel overwhelming to find the one that is right for you.