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:

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.