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Major Depression Information

(Prepared by, Dr. Brian Campbell, © 2013)




  • Major depression is the type of depression that will most likely benefit from treatment with medications

  • Major depression is more than just "the blues."

  • The condition lasts 2 weeks or more, and interferes with a person's ability to carry on daily tasks and enjoy activities that previously brought pleasure.

  • Major depression is associated with abnormal functioning of the brain.

  • An interaction between genetic tendency and life history appears to determine a person's chance of becoming depressed.

  • Episodes of depression may be triggered by stress, difficult life events, side effects of medications, or medication/substance withdrawal, or even viral infections that can affect the brain.

  • Depressed people will seem sad, or "down," or may be unable to enjoy normal activities.

  • They may have no appetite and lose weight (although some people eat more and gain more weight when depressed).

  • They may sleep too much or too little, have difficulty going to sleep, sleep restlessly, or awaken very early in the morning.

  • They may speak of feeling guilty, worthless, or hopeless

  • They may lack energy or be jumpy and agitated.

  • They may think about killing themselves, or may even attempt suicide.

  • Some depressed people have delusions (false, fixed ideas) about poverty, sickness, or sinfulness that are related to their depression.

  • Sometimes feelings of depression are worse at a particular time of day, for instance, every morning or evening.

  • Not everyone who is depressed has all these symptoms.



Antidepressants primarily work on brain chemicals called neurotransmitters, especially serotonin and norepinephrine.  Other antidepressants work on the neurotransmitter dopamine.  Scientists have found that these particular chemicals are involved in regulating mood, but they are unsure of the exact ways that they work.  The latest information on medications for treating depression is available on the U.S. Food and Drug Administration (FDA) website.

Popular newer antidepressants


Some of the newest and most popular antidepressants are called selective serotonin reuptake inhibitors (SSRIs).  Fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), paroxetine (Paxil), and citalopram (Celexa) are some of the most commonly prescribed SSRIs for depression.  Most are available in generic versions.  Serotonin and norepinephrine reuptake inhibitors (SNRIs) are similar to SSRIs and include venlafaxine (Effexor) and duloxetine (Cymbalta).

SSRIs and SNRIs tend to have fewer side effects than older antidepressants, but they sometimes produce headaches, nausea, jitters, or insomnia when people first start to take them.  These symptoms tend to fade with time.  Some people also experience sexual problems with SSRIs or SNRIs, which may be helped by adjusting the dosage or switching to another medication.

One popular antidepressant that works on dopamine is bupropion (Wellbutrin).  Bupropion tends to have similar side effects as SSRIs and SNRIs, but it is less likely to cause sexual side effects.  However, it can increase a person's risk for seizures.



Tricyclics are older antidepressants.  Tricyclics are powerful, but they are not used as much today because their potential side effects are more serious. They may affect the heart in people with heart conditions.  They sometimes cause dizziness, especially in older adults. They also may cause drowsiness, dry mouth, and weight gain.  These side effects can usually be corrected by changing the dosage or switching to another medication. However, tricyclics may be especially dangerous if taken in overdose.  Tricyclics include imipramine and nortriptyline.



Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressant medications. They can be especially effective in cases of "atypical" depression, such as when a person experiences increased appetite and the need for more sleep rather than decreased appetite and sleep. They also may help with anxious feelings or panic and other specific symptoms.

However, people who take MAOIs must avoid certain foods and beverages (including cheese and red wine) that contain a substance called tyramine.  Certain medications, including some types of birth control pills, prescription pain relievers, cold and allergy medications, and herbal supplements, also should be avoided while taking an MAOI.  These substances can interact with MAOIs to cause dangerous increases in blood pressure.  The development of a new MAOI skin patch may help reduce these risks.  If you are taking an MAOI, your doctor should give you a complete list of foods, medicines, and substances to avoid.

MAOIs can also react with SSRIs to produce a serious condition called "serotonin syndrome," which can cause confusion, hallucinations, increased sweating, muscle stiffness, seizures, changes in blood pressure or heart rhythm, and other potentially life-threatening conditions.  MAOIs should not be taken with SSRIs.


How should I take medication?


All antidepressants must be taken for at least 4 to 6 weeks before they have a full effect.  You should continue to take the medication, even if you are feeling better, to prevent the depression from returning.

Medication should be stopped only under a doctor's supervision.  Some medications need to be gradually stopped to give the body time to adjust.  Although antidepressants are not habit-forming or addictive, suddenly ending an antidepressant can cause withdrawal symptoms or lead to a relapse of the depression.  Some individuals, such as those with chronic or recurrent depression, may need to stay on the medication indefinitely.

In addition, if one medication does not work, you should consider trying another.  NIMH-funded research has shown that people who did not get well after taking a first medication increased their chances of beating the depression after they switched to a different medication or added another medication to their existing one.

Sometimes stimulants, anti-anxiety medications, or other medications are used together with an antidepressant, especially if a person has a co-existing illness.  However, neither anti-anxiety medications nor stimulants are effective against depression when taken alone, and both should be taken only under a doctor's close supervision.

More information about mental health medications is available on the NIMH website.

Report any unusual side effects to a doctor immediately.

FDA warning on antidepressants


Despite the relative safety and popularity of SSRIs and other antidepressants, studies have suggested that they may have unintentional effects on some people, especially adolescents and young adults.  In 2004, the Food and Drug Administration (FDA) conducted a thorough review of published and unpublished controlled clinical trials of antidepressants that involved nearly 4,400 children and adolescents.  The review revealed that 4 percent of those taking antidepressants thought about or attempted suicide (although no suicides occurred), compared to 2 percent of those receiving placebos.

This information prompted the FDA, in 2005, to adopt a "black box" warning label on all antidepressant medications to alert the public about the potential increased risk of suicidal thinking or attempts in children and adolescents taking antidepressants. In 2007, the FDA proposed that makers of all antidepressant medications extend the warning to include young adults up through age 24.  A "black box" warning is the most serious type of warning on prescription drug labeling.

The warning emphasizes that patients of all ages taking antidepressants should be closely monitored, especially during the initial weeks of treatment.  Possible side effects to look for are worsening depression, suicidal thinking or behavior, or any unusual changes in behavior such as sleeplessness, agitation, or withdrawal from normal social situations. The warning adds that families and caregivers should also be told of the need for close monitoring and report any changes to the doctor.  The latest information from the FDA can be found on their website.

Children, adolescents, and young adults taking antidepressants should be closely monitored.

Results of a comprehensive review of pediatric trials conducted between 1988 and 2006 suggested that the benefits of antidepressant medications likely outweigh their risks to children and adolescents with major depression and anxiety disorders.30 The study was funded in part by NIMH.

Also, the FDA issued a warning that combining an SSRI or SNRI antidepressant with one of the commonly-used "triptan" medications for migraine headache could cause a life-threatening "serotonin syndrome," marked by agitation, hallucinations, elevated body temperature, and rapid changes in blood pressure.  Although most dramatic in the case of the MAOIs, newer antidepressants may also be associated with potentially dangerous interactions with other medications.

What about St. John's wort?
The extract from the herb St. John's wort (Hypericum perforatum) has been used for centuries in many folk and herbal remedies. Today in Europe, it is used extensively to treat mild to moderate depression.  In the United States, it is one of the top-selling botanical products.

In an 8-week trial involving 340 patients diagnosed with major depression, St. John's wort was compared to a common SSRI and a placebo (sugar pill).  The trial found that St. John's wort was no more effective than the placebo in treating major depression.31 However, use of St. John's wort for minor or moderate depression may be more effective.  Its use in the treatment of depression remains under study.

St. John's wort can interact with other medications, including those used to control HIV infection.  In 2000, the FDA issued a Public Health Advisory letter stating that the herb may interfere with certain medications used to treat heart disease, depression, seizures, certain cancers, and those used to prevent organ transplant rejection. The herb also may interfere with the effectiveness of oral contraceptives.  Consult with your doctor before taking any herbal supplement.

Drug Interactions


If you are taking medications in addition to an antidepressant, make sure you tell your doctor about them.  Also, make sure you tell your doctor about any vitamins you are taking.  Vitamins, over-the-counter medications, and prescription medications can all interact in ways that could be harmful. 

In addition to telling your doctor about all vitamins, supplements, over-the-counter medications, and prescription medications, you should check for drug interactions by entering your information into a website that checks for drug interactions.

From the homepage menu, click on: Meds (located at the top of the page) 
In the table on the right, click on “Check Drug Interactions.”

If it appears that there are potential adverse interactions, print out the information and consult your physician.

Medications for Major Depression














Celexa (SSRI)













escitalopram (SSRI)





Luvox (SSRI)



Marplan (MAOI)



Nardil (MAOI)









Parnate (MAOI)



Paxil (SSRI)






Prozac (SSRI)
























Zoloft (SSRI)



Additional information can be obtained on individual medications by going to the following website link: