If one antidepressant isn’t treating your depression symptoms, you might want to explore combination therapies, such as stimulants or antipsychotics. These may benefit those with treatment-resistant depression.
If you have major depressive disorder (MDD), you may be taking an antidepressant.
Combination drug therapy is a type of treatment that many doctors and psychiatrists have been increasingly using during the past decade.
Until recently, doctors prescribed an antidepressant medication from only a single class of drugs, one medication at a time, called monotherapy.
Doctors generally start at a lower dosage and increase it before ruling it out as ineffective. If that happens, they might try another medication within that class or switch to another class of antidepressants entirely.
Bupropion
On its own, bupropion effectively treats MDD. But a doctor may also prescribe it with other medications for depression that is difficult to treat.
Bupropion is one of the most commonly used combination therapy medications. Medical professionals often use it with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
People who’ve experienced severe side effects from other antidepressant medications generally tolerate bupropion. It may also relieve some of the sexual side effects associated with some SSRIs and SNRIs.
Mirtazapine may be an option for people experiencing loss of appetite and insomnia. Its most common side effects are unintentional weight gain and sedation.
However, in-depth studies on its use as a combination medication aren’t available.
Antipsychotics
Research published in 2023 suggests atypical antipsychotics may effectively treat treatment-resistant depression. Food and Drug Administration (FDA) approved antipsychotics include:
- aripiprazole
- brexpiprazole
- extended-release quetiapine
- cariprazine
Current research also suggests a benefit of taking SSRIs and an antipsychotic for those with MDD with psychosis.
A
Antipsychotics, however, may have some
- unintentional weight gain
- changes in muscle control or movement (tardive dyskinesia)
- metabolic syndrome
Carefully consider the pros and cons of antipsychotics with your doctor. Their side effects may prolong or worsen some depression symptoms.
L-triiodothyronine
Some doctors use L-triiodothyronine (T3) in combination with SSRIs.
Research from 2021 suggests that T3 with an SSRI may lead to a faster response to treatment compared with taking an SSRI alone for older men. But more research is necessary.
The typical starting dose of T3 is 25 micrograms (mcg) daily. If that dosage doesn’t provide the desired results after 1 to 2 weeks, they may increase it to 50 mcg daily.
Stimulants
Dextroamphetamine (Dexedrine) and methylphenidate (Ritalin) are stimulants that medical professionals may use to treat depression. Doctors may prescribe them alone or in combination with antidepressant medications.
Many clinicians find that supplementing antidepressants with low doses of stimulants, such as methylphenidate, may help improve depression that doesn’t respond well to treatment.
However, not all clinical trials have shown benefits from this strategy.
Stimulants are most helpful when the desired effect is a quick response. People with severe depression symptoms or other conditions, such as chronic illnesses, may be good candidates for this combination.
Monotherapy’s success rates are low compared to combination therapy with a certain type of antidepressant. Many researchers and doctors believe combination treatments are a first-line approach to treating MDD and treatment-resistant depression.
Many doctors will still begin treatment with a single antidepressant medication. You’ll need to give it time to work before ruling it out as ineffective.
If the medication doesn’t work as desired after a trial period — usually about 6 to 8 weeks — your doctor may change your medication or add one to see whether the combination helps.