Medication for Depression: Types, Side Effects, and Management

What Is Depression?

Depression involves a low mood that can have an impact on energy, irritability, motivation, and general ability to function. Depression symptoms can be very individualized and depend on the type of depression someone is experiencing.

What Are Antidepressants?

Antidepressant medications work in the brain to increase levels of certain brain chemicals, which can lead to an improvement in symptoms for some people. Dopamine, serotonin, and norepinephrine are neurotransmitters (chemical messengers) that are most closely associated with depression. They affect mood, energy, and motivation.¹ People with depression are often found to be deficient in one or more of these chemicals, which at least partially explains their depression symptoms.

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.

Medication as Part of a Well-Rounded Depression Treatment Plan

Medication can be a helpful supplement in regard to treating depression; however, it’s typically not recommended as a stand-alone treatment.² Research has shown that medication is most effective when combined with evidence-based therapies like CBT for depression, interpersonal therapy, or EMDR for depression, and some people experience equivalent benefits from therapy alone.³

What to Ask Your Doctor About Antidepressants

The decision to start a new medication should always be made in collaboration with a doctor or other medical professional who can help you weigh the risks and benefits of taking an antidepressant. Your pharmacist and your doctor can help you with these questions.

Whenever a new medication is prescribed, it is important to ask your doctor about:

• 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, herbs, 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., antidepressant discontinuation syndrome)
• 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

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the most commonly prescribed type of antidepressant medication.² They are a first-line medication option for treating depression because they are generally effective and well-tolerated, with fewer risks and side effects vs. other antidepressants.^2,4 SSRIs work by blocking the reabsorption of serotonin, resulting in more available serotonin in the brain.⁵

Serotonin is closely related with mood, and people deficient in it are more likely to be depressed, sad, anxious, or moody.

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. A black box warning is the most serious warning from the FDA.

Side Effects of SSRIs

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.

More common side effects of SSRI medications can include:*⁵

• Headache
• Drowsiness
• Lack of sexual desire
• Erectile dysfunction
• Trouble reaching orgasm
• Changes in appetite and weight gain or weight loss
• Insomnia
• Nausea or GI upset
• Anxiety or irritability

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:*^5,6

• 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 ideation 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 (e.g., Prozac/fluoxetine withdrawal) or rebound depression or anxiety.⁵

Serotonin & 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.⁵ While serotonin affects mood, norepinephrine is developed in the adrenal glands and is more closely linked to energy levels and focus.

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. A black box warning is the most serious warning from the FDA.

Side Effects of SNRIs

SNRIs are similar to SSRIs because they both work on serotonin receptors. In addition to the common side effects of SSRIs, SNRIs can also cause other adverse effects.*⁵

Adverse side effects of SNRIs include:

• 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. People are recommended to taper off these medications under prescriber supervision.⁵

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 medications are ineffective.^2,4

TCAs work on multiple receptors in the brain, resulting in increased levels of both norepinephrine and serotonin.⁷ The only difference between tricyclic and tetracyclic antidepressants is how many rings are in their chemical structure (three vs. four).

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. A black box warning is the most serious warning from the FDA.

Side Effects of TCAs

TCAs are just as effective as SSRI and SNRI medications in treating depression but carry higher risks for serious side effects.

Side effects associated with TCAs can include:*⁷

• Dry mouth
• Constipation
• Dizziness
• Confusion
• Sedation
• Drops in blood pressure
• Weight gain and increased appetite
• Trouble urinating

More serious risks associated with TCAs can include:*⁷

• 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.⁸

With adverse effects similar to TCA’s, MAOIs are typically prescribed only when frontline SSRI and SNRI medications are ineffective.^2,4,5

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. A black box warning is the most serious warning from the FDA.

Side Effects of MAOIs

Common side effects of MAOIs can include:*⁸

• 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

In addition to these known side effects, MAOIs can sometimes carry the risk for more serious side effects, such as:*^6,8

• 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).

Common antidepressants that don’t fit in the four medication classes above include:⁵

• Bupropion (Wellbutrin)*: Wellbutrin is 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*: Trazodone an antidepressant that works by increasing serotonin, and is also often prescribed for insomnia
• Mirtazapine (Remeron)*: Remeron (mirtazapine) is an antidepressant that works to increase the amount of noradrenaline and serotonin in the brain
• Nefazodone*: Nefazodone is an antidepressant that works to increase the amount of serotonin in the brain
• Auvelity (dextromethorphan-bupropion)*: Auvelity (dextromethorphan-bupropion) is a brand new FDA-approved medication for treating depression in adults. This drug is the first FDA-approved medication targeting NMDA receptors, possibly opening new avenues for treatment-resistant depression.

Common Side Effects of Depression Medication

While antidepressants can be incredibly helpful, it’s important to know the risks and side effects before starting a new medication. Talk to your doctor and prescriber about any concerns you may have about antidepressant side effects.

Antidepressants & Suicide Risk

Antidepressants carry a black box warning for increased risk of suicidal thinking, feelings, and behavior in young people. This is part of why they require a prescription. 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 better understand how antidepressants may make you feel or how they may affect your symptoms to determine the best treatment for you.

Withdrawal Symptoms of Antidepressants

When discontinuing depression medication, it’s important to do so with guidance from your prescriber to ensure you are minimizing any withdrawal symptoms.

Antidepressant withdrawal symptoms may include:

• Mood swings
• Flu-like symptoms
• Restlessness
• Confusion
• Trouble sleeping
• Dizziness

You should never make a change to your medication dose or stop taking your medication before talking with your doctor. They will help to decide what is the correct dose for you and to develop a plan for you to safely change or discontinue your medication.

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).”

How Long Will You Have to Take Medication for Depression?

The length of time you may need to remain on medication will depend on individual circumstances and medical needs. Some may be advised to stay on medication for 6 months if it was their first depressive episode; however, those with major depression disorder and a history of multiple episodes may be advised to take it for 1-3 years or long-term.

The timeline of medication really is based on your unique symptoms, your history, and the way you adjust to the medication.

Can You Become Addicted to Antidepressants?

Unlike many other medications such as pain medication and sleeping aids, antidepressants are not habit forming. Antidepressants do not have an immediate impact, rather they work over a long period of time. As a result, the lack of immediate benefits doesn’t leave room for any habit-forming actions. While there can be symptoms of withdrawal if discontinuing antidepressants, antidepressants themselves are not habit forming, or addictive.

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. Several factors can play a role. For example, you may consider medications from different drug classes (SSRI vs SNRI), such as comparing Effexor vs Lexapro. Other factors such as age, condition being treated, and health history may influence this decision.

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.

The following factors might influence which medication a prescriber chooses to treat a person’s depression:^2,4,5

• 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 treatments 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.

Make Antidepressants Work for You: 6 Ways to Give Medication the Best Chance

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.

Here are six ways to give medication the best chance of working:

1. Attend 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.^2,3

2. Communicate 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.”

3. Work On 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.

4. Try Supplements & 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.

5. Sleep, Exercise, & Eat Well

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

6. 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.

Natural Treatment Options for Depression

If you’re looking to supplement your medication or for alternative treatments for depression, there are some natural options that can help lessen depression symptoms.

Here are examples of natural treatment options for depression:

• Positive lifestyle changes: improved diet, exercise, and sleep hygiene can help to minimize depression symptoms.
• St John’s Wort: St. John’s Wort comes from a plant and has many benefits that mimic those of SSRIs. However, it should not be taken with SSRIs. St John’s Wort has significant interactions with many medications, so ask your doctor before beginning taking St John’s Wort or any other herb or supplement.
• Light therapy: light therapy lamps mimic natural sunlight, which can improve mood and significantly help with seasonal affective disorder (SAD).

Final Thoughts on Medication for Depression

If you’ve been dealing with depression, you may want to talk to your doctor about medication. Especially when combined with therapy, antidepressants can make a big difference in your quality of life.