Major depressive disorder is a common mental health condition. Sadness, fatigue and low motivation are some of the symptoms of depression which interfere with a person’s ability to function. Antidepressants are medications that target certain brain chemicals related to depression, and some people find them helpful in reducing symptoms, especially when combined with therapy.
This article will provide an overview of each kind of antidepressant, how it works, and the potential benefits and the common side effects associated with it. The decision to start any new medication should always be made in collaboration with a doctor or other medical professional who can help you weigh these risks and benefits.
What Role Does Medication Play in Treating Depression?
Dopamine, serotonin, and norepinephrine are neurotransmitters (chemical messengers) which are most closely associated with depression, and these affect mood, energy, and motivation.7 People with depression are often found to be deficient in one or more of these chemicals, which at least partially explains their symptoms. Antidepressant medications work in the brain to increase levels of these chemicals, which can lead to an improvement in symptoms for some people.
Medication can be a helpful supplement to treatment for depression but is typically not recommended as a stand-alone treatment.1 Research has shown that medication is most effective when combined with evidence-based therapies like cognitive behavioral therapy (CBT) or Interpersonal therapy, but some people experience equivalent benefits from therapy alone.3 There are many individual factors that determine whether a person will respond to an antidepressant, and it often takes more than one trial to find a medication that works for them.
Even though depression is related to chemical imbalances in the brain, correcting these imbalances with medication only addresses one aspect of the disorder. All mental health disorders also cause changes in the way a person thinks, feels and behaves, which medication alone does not change. Developing healthy lifestyle habits, more effective self-care and coping skills, and addressing stress and problems in different areas of a person’s life are typically also important aspects of treating depression.
According to Kirsten Thompson, M.D. Psychiatrist and Founder of Remedy Psychiatry, “For many patients concerned or fearful about being on medication long-term, medication can be a temporary bridge to get to another point in life. Once starting medication, it generally takes 6-8 weeks to achieve a full response from the initial dose. The ideal medication dosage is the minimal effective dose (not just the lowest dose), with minimal side effects.
The minimal effective dose is the one in which symptoms are reduced or gone (remission), with a return to functioning in life. From there, it’s easier to then execute on life-improvement changes to further improve mood, such as getting out of toxic relationships, gaining employment or leaving a job, starting to eat better and exercise, and finding a therapist. Often life changes can improve and patients can elect to taper down and off medication in six to twelve months.”
Severe Warning for Antidepressants
Antidepressants carry a black box warning for increased risk of suicidal thinking, feelings, and behavior in young people. A black box warning is the most serious type of warning issued by the FDA. If you are concerned about this warning with taking an antidepressant, talk with your doctor to determine the best treatment for your situation.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most commonly prescribed type of antidepressant medication.1 They are a first-line medication option for treating depression because they are generally effective and well-tolerated, with fewer risks and side effects than other antidepressants.1,4 SSRIs work by blocking the reabsorption of serotonin, resulting in more available serotonin in the brain 8. Serotonin is closely related with mood, and people deficient in it are more likely to be depressed, sad, anxious or moody.
Some of the more commonly prescribed SSRIs used to treat depression include:
- Citalopram (Celexa)*
- Sertraline (Zoloft)*
- Escitalopram (Lexapro)*
- Fluoxetine (Prozac)*
- Paroxetine (Paxil)*
*This medication carries a black box warning for increased risk of suicide.
Generally, SSRIs are considered to have a low risk profile which is why they are usually the first type of medications prescribed to treat depression. Still, all medications carry some risks of adverse effects.
Some of the more common side effects of SSRI medications include:*8
- Headache
- Drowsiness
- Lack of sexual desire
- Erectile dysfunction
- Trouble reaching orgasm
- Higher or lower appetite
- Insomnia
- Nausea or GI upset
- Anxiety or irritability
*This is not a comprehensive list of side effects.
Some people experience all, some, or none of the common side effects as well as more serious side effects as a result of SSRI medications. These are more rare, but do occur in a small percentage of people.
Serious or life-threatening side effects of SSRIs can include:*2,8
- Serotonin syndrome: a serious condition that can result from too much serotonin being in the system. Symptoms include agitation, confusion, fever, dizziness, tremors, and marked changes in heart rate and blood pressure. Emergency medical care is required to treat this condition.
- Suicidal thoughts: Children, teens, and young adults (under 25) sometimes experience an increase in suicidal thoughts or urges after starting an SSRI. This rare side effect seems to mainly affect younger people and can occur even when there is no history of suicidal ideation.
- Tardive Dyskinesia: a rare disorder where a person suffers from uncontrollable movements or tics, usually associated with long-term use of antipsychotic drugs, but occasionally associated with SSRIs.
*This is not a comprehensive list of side effects.
Thompson states, “Typically starting at a low dose and titrating up is the best way to avoid severe side effects. Most side effects should be mild, so patients should always contact their prescriber with any severe side effects such as vomiting, insomnia or severe sedation, fevers, confusion or an increase in suicidal thoughts.”
People taking SSRI medications who become pregnant should consult with their prescriber once learning of their pregnancy as these may be harmful to the baby. Also, people who have been taking an SSRI are not advised to stop on their own. Some people who abruptly stop taking these medications experience withdrawal symptoms or rebound depression or anxiety.8
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
SNRIs are another commonly prescribed type of medication for depression, and these medications work on both serotonin and norepinephrine receptors in the brain.8 While serotonin affects mood, norepinephrine is developed in the adrenal glands and is more closely linked to energy levels and focus.
Some of the SNRI medications commonly prescribed to treat depression include:
- Desvenlafaxine (Pristiq)*
- Duloxetine (Cymbalta)*
- Levomilnacipran (Fetzima)*
- Venlafaxine (Effexor XR)*
*This medication carries a black box warning for increased risk of suicide.
SNRIs share many of the same side effects as SSRIs because they both work on serotonin receptors.
In addition to these common side effects, SNRI’s can also cause other adverse effects, including:*8
- Nervousness or anxiety
- Dry mouth
- Excessive energy levels
- Loss of appetite
- High blood pressure
- Increased suicidal ideation
*This is not a comprehensive list of side effects.
As with SSRI medications, women who become pregnant should notify their prescriber immediately for advice on whether to continue or stop the medication. Also, SNRIs also have the potential to increase suicidal thoughts in young people in the same way that SSRIs can. SNRI medications can also cause unpleasant withdrawal symptoms when people stop taking them abruptly, and people are recommended to taper off these medications under the supervision of their prescriber.8
Tricyclic & Tetracyclic Antidepressants (TCAs)
Tricyclic antidepressants are an older class of medications that were once commonly used to treat depression, and now are prescribed less often. TCAs carry higher risks for adverse effects and are often only prescribed when SSRI and SNRI treatment is ineffective.1,4 TCAs work on multiple receptors in the brain, resulting in increased levels of both norepinephrine and serotonin.5 The only difference between tricyclic and tetracyclic drugs is how many rings are in their chemical structure (three vs four).
Some of the TCAs prescribed to treat depression include:
- Amitriptyline*
- Amoxapine*
- Desipramine (Norpramin)*
- Doxepin*
- Imipramine (Tofranil)*
- Nortriptyline (Pamelor)*
- Protriptyline*
- Trimipramine*
*This medication carries a black box warning for increased risk of suicide.
TCAs are just as effective as SSRI and SNRI medications in treating depression but carry higher risks for serious side effects.
Some of the side effects associated with TCAs include:*5
- Dry mouth
- Constipation
- Dizziness
- Confusion
- Sedation
- Drops in blood pressure
- Weight gain and increased appetite
- Trouble urinating
*This is not a comprehensive list of side effects.
Some of the more serious risks associated with TCAs include:*5
- Cardiac problems (can be fatal)
- Seizures (for those with epilepsy)
- Increased suicidal ideation (in those under age 24)
- Serotonin syndrome
- Withdrawal symptoms (when stopped abruptly)
- Birth defects (in the eyes, ears, neck, and face)
*This is not a comprehensive list of side effects.
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs are the oldest type of antidepressant medications. They work by blocking a particular enzyme responsible for clearing out excess serotonin, norepinephrine, and dopamine from the brain.(6) By blocking this enzyme (monoamine oxidase), MAOIs make these chemicals more available to the brain, helping with deficiencies associated with depressive symptoms.6 With adverse effects similar to TCA’s, MAOIs are typically prescribed only when frontline SSRI and SNRI medications are ineffective.1,4,8
MAOIs commonly prescribed to treat depression include:
- isocarboxazid (Marplan)*
- phenelzine (Nardil)*
- selegiline (Emsam)*
- tranylcypromine (Parnate)*
*This medication carries a black box warning for increased risk of suicide.
Some of the common side effects of MAOIs include:*6
- Dizziness
- Headache
- Dry mouth
- Nausea
- Diarrhea or constipation
- Sleep problems (drowsiness or insomnia)
- Skin rashes
- Trouble urinating
- Lowered sexual desire
- Difficulty reaching orgasm
- Weight gain
- Muscle cramps, tics or jerking
- Tingling skin
- Weight gain
- Lowered blood pressure
*This is not a comprehensive list of side effects.
In addition to these known side effects, MAOIs can sometimes carry the risk for more serious side effects, such as:*2,6
- Increased risk for suicidal ideation (particularly in younger people)
- Tardive dyskinesia
- Dangerous interactions with certain foods and medications which can cause spikes in blood pressure
- Serotonin syndrome
- May be harmful to unborn babies when exposed in-utero
- Dangerous withdrawal symptoms when stopping abruptly which can include the risk for convulsions, psychosis, or flu-like symptoms
*This is not a comprehensive list of side effects.
Other Medications for Depression
While most antidepressant medications fall within one of the above categories, there are a few outliers. Some medications prescribed for depression are atypical in their mechanism of action but result in the same neurotransmitter activity in the brain. These medications all work on one or more of the three neurotransmitters most closely involved in depression (serotonin, dopamine and norepinephrine).
Some of the more common antidepressants that do not fit in the four medication classes above include:8
- bupropion (Wellbutrin)*: an antidepressant that works on norepinephrine and dopamine receptors and is also prescribed for smoking cessation, ADHD, and for those concerned about weight gain as a side effect
- trazodone*: an antidepressant that works by increasing serotonin, and is also often prescribed for insomnia
- mirtazepine (Remeron)*: an antidepressant that works to increase the amount of noradrenaline and serotonin in the brain
- nefazodone*: an antidepressant that works to increase the amount of serotonin in the brain
*This medication carries a black box warning for increased risk of suicide.
Is Medication Right for You?
If you struggle with depression, you are probably trying to determine whether to try an antidepressant and if so, which one might be right for you. It is important to note that all medications carry some risks of side effects, and also that medication isn’t the right option for everyone. Also, many people need to try more than one medication before finding one that works for them, and because antidepressants often take up to 4-6 weeks to work, these trials can take several months.1,4,8
In short, antidepressants aren’t a magic cure for depression, and may not provide immediate relief. In fact, research on the effectiveness of therapy vs medication for the treatment of depression has found that people treated with medication only do not experience the lasting gains as those who engage in therapy. In many instances, therapy can be as effective or more effective than therapy, even as a standalone treatment for depression.3
Antidepressants only target the neurochemical aspect of depression, without helping people find out if there is a deeper issue or root cause. People who take antidepressants also do not learn how to cope with and manage their symptoms.3 Because depression is usually chronic in nature, even those on medication often experience periods where their symptoms worsen, making it important that they develop alternative methods of coping.
Some additional things to consider when making the decision to try an antidepressant include:1,4
- How severe your symptoms are, and how much they are interfering with your life
- What other options you have already tried (i.e. therapy, lifestyle changes)
- How you feel about medication in general and prior experience you’ve had with it
- What expectations you would have of how medication could help
- Whether you are willing to risk the possibility of adverse side effects
- Your willingness to engage in therapy before, after, or instead of starting medication
- Your willingness to attend follow up appointments with the provider, and to try a different medication or treatment if it is not working
When Can I Expect to Feel Better After Beginning a New Medication?
According to Thompson, “Many medications for daily anxiety and depression (such as the SSRIs and SNRIs) take 3-6 weeks to start working. Even then, studies show that some patients are late responders and may have improved response up to 8-12 weeks after starting a medication. Patience is important. But in some cases, the dose may still be too low, or the patient may not be responding. In these cases, it’s important to have a conversation with the prescriber to determine an appropriate next step. This might include increasing the dose, changing the medication, or adding an augmenting agent (which is another medication to improve the response beyond that of the first medication).”
Determining the Right Antidepressant Medication
Treatment decisions should be the result of collaboration between you and your provider, and it is important to play an active role in your treatment plan. Those who decide to try an antidepressant medication should defer to the knowledge and expertise of a prescriber, but also should provide their prescriber with all the information needed to make a recommendation.
Some of the following factors might influence which medication a prescriber chooses to treat a person’s depression:1,4,8
- Age: Medication is typically not recommended as a frontline treatment for children, teens, and even older adults with depression because of unique adverse effects that can occur. Certain antidepressants carry higher risks of these age-related risk factors.
- Symptom severity: Major depressive disorder is diagnosed as either mild, moderate, or severe, depending on the number of symptoms reported by the patient. The severity of symptoms helps the provider determine recommendations for treatment.
- Other medications: All medications have the potential to interact with other prescribed drugs, sometimes in unexpected ways. Those on medications should inform the provider to help guard against adverse effects or interactions.
- Treatment history: When a person has tried one or more treatment for depression (therapy or medication) in the past, knowing what was helpful and unhelpful can be important in helping the provider make treatment recommendations.
- Medication compliance: Certain antidepressant medications can cause dangerous withdrawals or rebound symptoms when a person stops taking them abruptly. Let the provider know if you have been noncompliant or inconsistent with medication in the past.
- Substance use: Some medications prescribed for depression carry risks for abuse and addiction. If you have struggled in the past with addiction, it is important to let the provider know. Also, if you are currently abusing any substances recreationally (even alcohol), you should ask about potential interactions with any newly prescribed medications.
- Specific symptoms: Not everyone who has depression has the same symptoms, and different medications can be recommended for targeting specific symptoms. Make sure you discuss your symptoms with the provider, emphasizing those causing the most impairment for you.
- Response to treatment: Getting a prescription for an antidepressant is just the beginning of treatment and follow up appointments are important. These appointments help the provider determine whether the medication is working or not. Make sure to attend scheduled follow-ups and to speak up about whether your symptoms are improving, as well as mentioning any side effects. Based on your report, adjustments may be made.
- Patient preference: If you have a strong preference for what kind of treatment or medication you receive, let the prescriber know. Your input is important, and any treatment decisions should be made collaboratively with you and the provider.
Your prescriber should not be the only one asking questions and getting information in initial and follow up visits.
Whenever a new medication is prescribed, it is important to understand:
- The way the medication works and why it was selected over other options
- The possible side effects of the medication and which are most common
- Any side effects that require medical attention
- Any possible interactions with other medications, drugs, or supplements
- The dosage you are on relative to the maximum dose
- How and when to take the medication (i.e. night or morning, with food or not)
- What to do if you miss a dose (i.e. wait until next dose or not)
- What can happen if the medication is stopped (i.e. any withdrawal symptoms)
- How long the drug takes to work and what to monitor to determine if it is working
- When a follow up appointment should be made to determine if the drug is working
Your pharmacist and your doctor can help you with these questions when you pick up your prescribed medication.
Tips for Making Antidepressants Work
Each person is unique, and may respond differently to different drugs, even ones within the same class of medication. It is not uncommon for a person to try more than one antidepressant before finding one that works for them. You cannot control which drugs will work for you and which will not, but there are some lifestyle changes you can make to help manage your depressive symptoms.
Making the following changes can help ensure that you do not misidentify side effects, and also help you give the medication the best chance of working:
Therapy
Therapy can help identify and address root issues of depression and teach more effective methods of coping. A combination of medication and therapy is most likely to provide lasting improvements in symptoms.1,3
Communicating With Your Care Team
Thompson suggests, “After starting a medication, a patient should have follow-up appointments at regular intervals (typically every 3-5 weeks when medications are added or dosages are changed). As it can be hard to remember, It can sometimes help for patients to write a list of benefits or side effects they’ve noted during that time, to report back to their provider. Additionally, if a patient has a therapist and prescribing physician or nurse practitioner, signing a release so that the prescriber and therapist can collaborate in care can ultimately help the patient achieve a more coordinated treatment effort.”
Sobriety
Taking a break from alcohol and recreational drugs is often recommended after starting a new medication. This helps to lower the risk of adverse effects or interactions, and helps you establish whether the medication is working.
Supplements and OTC Medications
Certain vitamins, supplements, and over the counter medications can interfere or interact with prescribed antidepressants. Make sure to talk to your doctor about anything you take and consider taking a break from these if there is a possibility of a negative interaction. That way, you can be sure that side effects are from the medication, and not from an interaction.
Sleep, Exercise, & Nutrition
Eating well, sleeping enough, and getting adequate exercise form the basis of a healthy lifestyle, and are important for all aspects of your physical and mental health. Remaining consistent with healthy routines will help ensure that side effects are not the result of poor lifestyle habits like not sleeping enough or overeating. Certain types of exercise like yoga have more research supporting their ability to reduce depressive symptoms.4
Follow a Routine
The goal of medication is to improve a person’s ability to function in their daily lives so following your normal routine is important to establish whether the medication is working. Pushing through low energy, motivation and mood can be challenging, but not doing so tends to worsen symptoms, counteracting any effects of the medication.
Additional Information & Resources on Depression Treatment
SAMHSA: the Substance Abuse and Mental Health Services Administration is a governmental institution that provides information, resources, and help connecting with a treatment provider.24 Hour Helpline: 1-800-662-HELP (4357)
NAMI: the National Alliance on Mental Health is a nonprofit dedicated to supporting people who struggle with mental illness. Their site has information on different types of mental illness (including depression) as well as providing assistance to people looking for treatment or a support group.
