Different Types of Depression Medication

The different types of medication used to treat depression

Medication choices include many medication within the following classes:

  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Others

TCAs and MAOIs

TCAs and MAOIs are the oldest antidepressants. They are effective treatments but have many problematic side effects. In addition, they can be unsafe to use in patients with certain medical conditions and in older persons. MAOIs require strict adherence to a dietary plan that is free of tyramine. Although these medications are effective for treatment of depression, they are now typically reserved for use after a person’s symptoms have not improved on one of the newer medications available. The most commonly prescribed TCAs are desipramine and nortriptyline because of their better tolerated side effect profiles.


The first SSRI to enter the market was fluoxetine (Prozac) in the late 1980s. Because of its low side-effect profile relative to the TCAs and MAOIs, fluoxetine quickly became the most popular antidepressant. Several SSRIs have come on the market since. Because SSRIs as a group are the most commonly prescribed antidepressants, the decision as to choice of medication is often in deciding between the SSRIs available. There is no good evidence that any SSRI is better than another in the treatment of depression or any of the anxiety disorders. The choice of SSRI has more to do with side profiles and potential drug interactions. Discontinuation syndromes are least likely from fluoxetine and are more likely from paroxetine. Fluoxetine may be a better choice for someone who tends to miss doses of medication. On the other hand, because of its long half-life, adverse effects will take longer to dissipate after discontinuation of the drug. In terms of potential interactions with other medications, fluoxetine, paroxetine, and fluvoxamine have the highest potential for such interactions. Sertraline, citalopram, and escitalopram have a lower risk for interactions. Cost may be a factor in medication choice as well, with fluoxetine and paroxetine being available in generic forms.

Other Depression Medications

Medications classified under “others” have various mechanisms of action. Bupropion blocks the reuptake of dopamine and norepinephrine. Bupropion does not have significant drug–drug interactions and is not associated with sexual dysfunction. Venlafaxine and duloxetine are dual reuptake inhibitors of both norepinephrine and serotonin (and to a lesser extent, dopamine). They have similar side effect profiles to the SSRIs but have the advantage of working through two neurotransmitter systems. Mirtazapine causes increased levels of serotonin and norepinephrine by blocking the inhibition of their release (both serotonin and norepinephrine act to turn off their own release by interacting with receptors on the sending neuron). Trazodone and nefazodone are chemically similar (trazodone is an older antidepressant), blocking serotonin reuptake as well as blocking some types of serotonin receptors directly. Trazodone is very sedating and is mainly used for insomnia, and nefazodone is not first-line because of its association with some cases of liver failure.


Typically, the first decision regarding antidepressant choice is between the newer classes. All antidepressants are effective for depression, but the choice of type will likely depend on side-effect profiles, patient characteristics, physician preference, and cost. Some insurance plans have formularies restricting use to a specific medication. In these circumstances, the physician would need to explain the rationale for choosing a non-formulary medicine over a formulary one.

In addition to antidepressants, many other medications are used in the treatment of depression: anticonvulsants, antipsychotic, and benzodiazepines. Typically, these medications are used to address specific co-morbid conditions or symptoms that are not addressed by the antidepressant. In cases of partial response to an antidepressant, there may be medications prescribed for augmentation, including buspirone, thyroid hormone, or even a stimulant such as methylphenidate.