Medication for Kids With Depression

For kids with depression, experts agree that the first choice in medication treatment is the group of anti-depressant medications called SSRIs — selective serotonin reuptake inhibitors. And if the first SSRI a child is prescribed is not successful in combatting depression, they recommend trying another one, since individual kids respond differently to different SSRIs.

But before we say more about antidepressants, it’s important to keep in mind that not all kids who are depressed need to be treated with medication. For children and teenagers whose depression symptoms are mild, therapy is the recommended first choice. There are several kinds of therapy, including cognitive behavior therapy (CBT) and interpersonal therapy (IPT), that have been shown to be effective for kids with depression. If there’s no response with the therapy over a period of 12 weeks — or these therapies are not available — then SSRI medications should be considered.

For kids with moderate to severe depression, an SSRI is usually recommended, either alone or in combination with therapy. For kids with severe symptoms, starting with combined therapy and medication is recommended. “Depression is serious and it can take one’s life,” notes Sarper Taskiran, MD, a child and adolescent psychiatrist at the Child Mind Institute. “It needs to be treated effectively and robustly.”

The approach to medication treatment for each child varies, says Dr. Taskiran, because many children develop depression as a result of other challenges they are facing, including anxiety and ADHD. If they are treated only for depression, without recognizing the underlying problems, the treatment may not be effective.

So the first task for a clinician prescribing medication is to decide whether any other conditions need to be treated at the same time. In the period since the pandemic lockdown, Dr. Taskiran says, he’s seeing many young patients who had been dealing with anxiety or ADHD before who developed depression as their struggles compounded.

“I think, as clinicians, we need to be very careful not to just jump into treating depression as if it is something that happened just now,” he adds, “but examine the child’s history, the unfolding of the symptoms, so that we can address their needs.

Antidepressants usually work by balancing the levels of neurotransmitters — chemicals that send signals between neurons — in the brain. These chemicals include serotonin, dopamine, and norepinephrine. Higher levels of these chemicals usually correspond with lower levels of depression.

SSRIs work by increasing the availability of serotonin in the brain. They are the first choice of medication for children and adolescents with depression because they have been shown to be effective in reducing symptoms and they have fewer problematic side effects than other kinds of antidepressants.

Another closely related category of antidepressant is SNRIs, or serotonin and norepinephrine reuptake inhibitors. Since SNRIs affect two kinds of neurotransmitters, they tend to produce more side effects, and are usually considered after SSRIs have been tried.

SSRIs and SNRIs usually take four to six weeks to have an effect on depression symptoms, and their effectiveness continues to grow for several more weeks after that. The best dose — the most reduction of symptoms without problematic side effects — varies from child to child. So the doctor should start with a low dose and work up gradually.

There are several different SSRI medications a doctor might recommend as their first choice for a depressed child. Only two, fluoxetine (Prozac) and escitalopram (Lexapro), have FDA approval for treatment of depression in children or teens. Fluoxetine is approved for kids 8 and up, and escitalopram for those 12 and up.

Fluoxetine is the most studied of the SSRIs — its effectiveness in kids has been confirmed by major studies — and it is the SSRI most often prescribed for teenagers and children with depression.

Other antidepressants have been approved for use in children but not specifically for depression. Sertraline (Zoloft) and Fluvoxamine (Luvox) are FDA approved for children with OCD (sertraline 6 and older, and fluvoxamine 8 and older). Duloxetine (Cymbalta), which is an SNRI, has FDA approval for anxiety in children and adolescents. All of these are also used for depression.

Doctors usually start by prescribing an SSRI that has been FDA approved for some use (if not depression) in children and teenagers. But if that isn’t successful, they may try other SSRIs that have FDA approval in adults, though not children. This is called “off-label” use of the medication.

Lack of FDA approval for use in kids doesn’t mean that a medication hasn’t been thoroughly tested in clinical trials with kids. It reflects the fact that once a drug is approved for use in adults, the company that makes it often chooses not to go through the expensive FDA approval process again for use in kids.

In the case of anti-depressants, including those that don’t have FDA approval, other researchers have amassed a large body of evidence, including double-blind studies, for their safety and effectiveness for children and teens.

The SSRIs most commonly prescribed in children and teenagers are:

• Fluoxetine (Prozac)
• Escitalopram (Lexapro)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Fluvoxamine (Luvox)
• Paroxetine (Paxil)

SNRIs:

• Duloxetine (Cymbalta)
• Venlafaxine (Effexor)

Side effects of SSRIs and SNRIs are usually relatively mild, compared to other medications. They are usually experienced during the first few weeks, and they decline over time. Clinicians should be in close touch with families during these first several weeks, monitoring how children are feeling and any changes in their behavior.

If side effects don’t decline and they’re making a child uncomfortable, it’s appropriate for the doctor to prescribe a different SSRI. Children who experience unpleasant side effects on one SSRI often respond differently to another.

Side effects can include:

• Nausea, vomiting or diarrhea
• Stomachaches
• Headache
• Drowsiness
• Dry mouth
• Insomnia
• Nervousness, agitation, or restlessness
• Activation — increasing irritability and impulsiveness
• Dizziness
• Reduced sexual desire
• Impact on appetite, leading to weight loss or weight gain

SSRIs and SNRIs come with what’s called a “Black Box” warning from the FDA that children and adolescents taking them may experience an increased risk of suicidal thoughts. These medications have not been linked to attempted or completed suicides, but it’s recommended that clinicians and parents monitor kids taking them for any worsening in depression or emergence of suicidal thinking as they are adjusting to a new medication.

More recent research has not supported the increased risk of suicidal thoughts, Dr. Taskiran notes, and most experts conclude that the benefits of SSRIs outweigh the risks. Some research has found that suicide rates in children decrease when they take antidepressants.

Some other antidepressants are used to treat children when SSRIs aren’t effective for them, or when they have problems with side effects.

Bupropion (Wellbutrin) is an antidepressant that is called an NDRI (norepinephrine/dopamine-reuptake inhibitor). It works by increasing the availability in the brain of neurotransmitters norepinephrine and dopamine. Bupropion is FDA approved for depression in adults, but not in kids. Bupropion is prescribed off-label for kids with ADHD, and it can also be used for depression. It is sometimes added to an SSRI when the SSRI alone isn’t providing enough relief from symptoms. Adding buproprion can help ease sexual side effects of the SSRI if that is a concern for the adolescent.

There are several newer antidepressants that are FDA-approved for treatment of depression in adults, but they have not been studied extensively in children and adolescents. They are sometimes prescribed off-label, Dr. Taskiran explains, when kids have problems with side effects on SSRIs, particularly weight gain and sexual side effects.

One of them, mirtazapine (Remeron), is in a group of medications called tetracyclic antidepressants (TeCAs). By inhibiting a particular set of receptors in the brain, Mirtazapine causes an increased release of serotonin and norepinephrine.

Another, Vilazodone (Viibryd), increases the effect of serotonin in the brain in two ways — by slowing its removal and by stimulating serotonin receptors. Because of this dual activity, it is called a serotonin partial agonist–reuptake inhibitor (SPARI) and is expected to have more robust anti-anxiety action.

Because more than a third of kids — between 55 and 65 percent — don’t respond  to the initial antidepressant they take, it’s not unusual to try a second medication. Kids who don’t respond to the first often do find success with a different antidepressant. Therapy may also be added if it hasn’t been tried.

If a child does not have a clear response to the medication — about a 40 percent reduction in symptoms — after six weeks, a switch should be made, Dr. Taskiran says. “If we’re not seeing that, it’s not worthwhile to keep the patient on the same medication.”

But he emphasizes that a medication should not be rejected until it’s been tried for the full six weeks.

In a rush for improvement, he notes, a medication will sometimes be judged ineffective after just two weeks, and kids will be switched to a second choice. But two weeks isn’t enough time for an SSRI to become fully effective, so medications that are potentially useful can be discarded too quickly. “It’s really important that we give these medications enough of a chance, from a time perspective and a dose perspective, to be effective.”

Of the kids who are switched to a second medication, he says, 60 percent of them respond to the second medication. “For those who are still non-responders,” Dr. Taskiron says, “we need to add either mood stabilizers or atypical antipsychotics to increase the remission rate.”

Of the mood stabilizers, lithium has been approved by the FDA for use in teenagers and children. Among atypical antipsychotics, aripiprazole (Abilify) and risperidone (Risperdal) are the ones that are most studied and most often used in kids, and they are FDA approved for some uses in kids. Aripiprazole is often the first choice because it has fewer problematic side effects than lithium or risperidone.

If a second medication isn’t successful, Dr. Taskiran notes that it’s also important to look at the diagnosis again, to consider whether there might be other factors going on that are affecting the outcome. “We know that family conflict, drug and alcohol use, and comorbid disorders are sometimes the culprit, and when we address those, we can get a better remission.”

When teenagers or children are treated successfully with an antidepressant, experts advise that they stay on the medication for nine months to a year after their symptoms are gone to prevent a relapse. “This is usually the time that is needed for the brain to correct the chemical imbalances that result in depression,” Dr. Taskiran explains.

If there’s a relapse after the child has tapered down and gone off the medication, longer treatment may be needed to help prevent recurrence.

About one in three kids treated for depression, he adds, will need more time on the medication. “After two years, we can stop the medication again, cautiously and carefully. But if we see another relapse, a second relapse, continuing on SSRIs indefinitely may be the best course.” 

For children and teenagers, getting a diagnosis of depression can be a relief, because they understand that the way they are feeling is not a permanent condition. “Depressed kids are often thinking that there is something inherently wrong with them,” Dr. Taskiran explains, “that they are built this way, and that’s the core belief that leads to suicidal ideation. They think they are flawed and that’s why they give up on themselves so easily.”

When they understand that this is a disorder that can be treated, they usually welcome it. In his experience, he says, most are comfortable with the idea of medication.  

Having said that, he adds, teenagers need parental support to make sure they are compliant with treatment. “They’re kids. No 14-year-old should be responsible to remember to take their medication every day.”

Dr. Taskiran notes that success in treatment depends on the patient, the parents, and the provider all being on the same page. “I usually tell parents, ‘Look, we need to have a trusting relationship and you need to be on board with the process that is your child’s treatment in order for this to work.’ “