Medications for Major Depression – Types, Effects, and Approaches

The first medication used to treat depression was "discovered" while researchers were studying another medical disorder. Iproniazid was originally developed as a treatment for tuberculosis in the 1950's. Once it became clear that antidepressant medications were possible, medical science focused attention towards researching and developing depression-specific medications (as well as many other medications useful for treating mental illness).

Antidepressants are used most widely for serious depressions, but they can also be helpful for some milder depressions. Antidepressants, although they are not "uppers" or stimulants, take away or reduce the symptoms of depression and help the depressed person feel the way he did before he became depressed.

Antidepressants are also used for disorders characterized principally by anxiety. They can block the symptoms of panic, including rapid heartbeat, terror, dizziness, chest pains, nausea, and breathing problems. They can also be used to treat some phobias.

Modern antidepressant medications are thought to have their effect based on their ability to alter the balance of neurochemicals and neurochemical receptors at the synapse level within the brain. Selective serotonin reuptake inhibitors (SSRIs) and their newer antidepressant cousins, the serotonin norepinephrine reuptake inhibitors (SNRIs), are today considered first choice medication treatment for the treatment of Major Depression. Other medications, including the older tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are used as second-line choices.

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Four groups of antidepressant medications are most often prescribed for depression:
  • Selective serotonin reuptake inhibitors (SSRIs) act specifically on the neurotransmitter serotonin. They are the most common agents prescribed for depression worldwide. These agents block the reuptake of serotonin from the synapse to the nerve, thus artificially increasing the serotonin that is available in the synapse (this is functional serotonin, since it can become involved in signal transmission, the cardinal function of neurotransmitters). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox).
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs) are the second-most popular antidepressants worldwide. These agents block the reuptake of both serotonin and norepinephrine from the synapse into the nerve (thus increasing the amounts of these chemicals that can participate in signal transmission). SNRIs include venlafaxine (Effexor) and duloxetine (Cymbalta).
  • Bupropion (Wellbutrin) is a very popular antidepressant medication classified as a norepinephrine-dopamine reuptake inhibitor (NDRI). It acts by blocking the reuptake of dopamine and norepinephrine.
  • Mirtazapine (Remeron) works differently from the compounds discussed above. Mirtazapine targets specific serotonin and norepinephrine receptors in the brain, thus indirectly increasing the activity of several brain circuits.
  • Tricyclic antidepressants (TCAs) are older agents seldom used now as first-line treatment. They work similarly to the SNRIs, but have other neurochemical properties which result in very high side effect rates, as compared to almost all other antidepressants. They are sometimes used in cases where other antidepressants have not worked. TCAs include amitriptyline (Elavil, Limbitrol), desipramine (Norpramin), doxepin (Sinequan), imipramine (Norpramin, Tofranil), nortriptyline (Pamelor, Aventyl), and protriptyline (Vivactil).
  • Monoamine oxidase inhibitors (MAOIs) are also seldom used now. They work by inactivating enzymes in the brain which catabolize (chew up) serotonin, norepinephrine, and dopamine from the synapse, thus increasing the levels of these chemicals in the brain. They can sometimes be effective for people who do not respond to other medications or who have “atypical” depression with marked anxiety, excessive sleeping, irritability, hypochondria, or phobic characteristics. However, they are the least safe antidepressants to use, as they have important medication interactions and require adherence to a particular diet. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate).
  • Non-antidepressant adjunctive agents. Often psychiatrists will combine the antidepressants mentioned above with each other (we call this a “combination”) or with agents which are not antidepressants themselves (we call this “augmentation”). These latter agents can include the atypical antipsychotic agents [aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), risperidone (Risperdal)], buspirone (Buspar), thyroid hormone (triiodothyonine, or “T3”), the stimulants [methylphenidate (Ritalin), dextroaphetamine (Aderall)], dopamine receptor agonists [pramipexole (Mirapex), ropinirole (Requipp)], lithium, lamotrigine (Lamictal), s-adenosyl methionine (SAMe), pindolol, and steroid hormones (testosterone, estrogen, DHEA).
Antidepressants are medications and like all medications, they should be used only as prescribed by a physician. Medications can be dangerous and even lethal when taken in a haphazard manner. For example, specific antidepressants are considered unsafe for pregnant or nursing women. You should only obtain medication from a reputable drugstore and only as indicated on a prescription notice from your doctor. Any concerns about the safety of particular medications should be discussed with your doctor.

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Even though antidepressants impact a person's levels of neurotransmitters within hours, they usually take several weeks to exert a noticeable effect on mood. This is because antidepressant drugs are thought to cause new receptors to grow within the synapses, and this growth process takes a few weeks. As a result, the effects of antidepressant medications are not instantly apparent, but may take several weeks to build up to levels that impact someone's mood. When treatment effects occur, they occur gradually.

Patients often fail to notice the positive effect that the medication is having, but generally family and friends will notice. It is important to keep taking an antidepressant as prescribed for several weeks before making a decision about whether or not it is effective. Up to six weeks may be required to know if a drug will work.

You may have to try several different antidepressant medications before finding one that works well. Even within a family of similar antidepressant medications, some people do better with one than with others. Decisions about when it is time to try new medications are best made when the patient, physician, and the psychotherapist (if one is present) work together as a team. Depressed patients often discount or ignore positive changes brought about by antidepressant medication. Health care professionals can counter this tendency to ignore positive change by offering their more objective observations, while patients can contribute their own impression regarding positive effects and troubling side-effects.

The dosage of antidepressants varies, depending on the type of drug, the person's body chemistry, age, and, sometimes, body weight. Dosages are generally started low and raised gradually over time until the desired effect is reached without the appearance of troublesome side effects.

Many people are concerned about having to take antidepressants for the rest of their lives. Typically, individuals begin taking antidepressants when their depression is at its worst. The medication, combined with psychotherapy, will allow most people to get to a point where they can gradually decrease or discontinue their use of antidepressants and maintain well-being by using skills learned in psychotherapy. However, for those individuals whose depression returns when they stop using medication, long-term use of antidepressants may be essential.

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