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Antidepressants: Do they work?
ConsumerReportsHealth.org provides comprehensive, easy-to-read explanations about why antidepressants work, and exactly how they help counter symptoms of depression.
When you need to make important decisions about your health and the health of your loved ones, you need information from experts who have your interests, as a consumer, in mind - just the facts, no drug company advertising. ConsumerReportsHealth.org is your essential resource for trusted, unbiased, independent health information, available 24 hours a day, 7 days a week.
There's good research showing that these drugs work for people with depression. But they can cause unpleasant side effects. If your depression is mild, you may decide with your doctor that they aren't for you.

We don't know for sure how antidepressants compare with another good treatment called cognitive therapy. But if you have mild or moderate depression, cognitive therapy may work slightly better.1 2
What are they?

Doctors use three main types of antidepressant to treat depression. Here are their names.
  • Selective serotonin reuptake inhibitors (SSRIs). Generic names (with brand names) include fluoxetine (Prozac, Sarafem), fluvoxamine, paroxetine (Paxil), sertraline (Zoloft) and citalopram (Celexa).
  • Tricyclic antidepressants (TCAs). Some examples of TCAs are amitriptyline, desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor) and trimipramine (Surmontil).
  • Monoamine oxidase inhibitors (MAOIs). Examples of MAOIs are phenelzine (Nardil) and tranylcypromine (Parnate). This type of antidepressant isn't used very much any more.
Other antidepressants include bupropion (Wellbutrin), trazodone (Desyrel), venlafaxine (Effexor) and reboxetine. Reboxetine is not available in the United States.

Your doctor will help you find an antidepressant that suits you. You'll probably need to take antidepressants for more than six weeks before you start to feel better. So it's important not to stop taking them early.
How can they help?

Antidepressants can help you with the symptoms of depression.

Between half and two-thirds of depressed people feel much better after treatment.3 4 5 6 7 8 9 10

Taking an antidepressant can mean:
  • You feel less sad, hopeless, worried or guilty
  • Your appetite improves
  • Your sex drive comes back
  • You can concentrate better
  • You no longer think about suicide.
The different types of antidepressant all seem to work as well as each other.7 9 11 12 13 14 But venlafaxine works slightly better than SSRIs in people with mild or moderate depression.13

Your symptoms should start to get better within four weeks to 12 weeks of starting antidepressants.

MAOIs aren't used very often, but they may work better in people with unusual symptoms. Depression with unusual symptoms is called atypical depression. People with atypical depression tend to eat and sleep more than usual. People with typical depression eat and sleep less.15
How long should I stay on antidepressants?

We don't know for certain how long you should stay on antidepressants. But specialists recommend that you take antidepressants for at least four months to six months after you start to feel better.16 That's because:
  • Depression often comes back sooner or later after you stop treatment. This is called a relapse
  • About 6 in 10 people who stop taking their antidepressants after a few months get depressed again within a year
  • Staying on antidepressants for at least six months after you start to feel better can reduce your chances of a relapse
  • In studies, only 2 in 10 people who stayed on antidepressants got depressed again during treatment. People in these studies stayed on antidepressants for six months to three years after they felt better.16 17 18
Long-term treatment with antidepressants works, but you'll continue getting side effects. About 1 in 5 people have to stop long-term treatment because of side effects.16
Why should they work?

Antidepressants affect chemicals called neurotransmitters which help carry messages from brain cell to brain cell. In particular, antidepressants boost the amounts of the chemicals serotonin and norepinephrine. This gradually causes changes in how your brain cells behave. It can take several weeks before you can tell if the drugs are affecting your mood.

The problem is that the drugs also affect other brain cells, disrupting nerve signals and causing side effects.
Can they be harmful?

All antidepressants can cause side effects. It's important to find the drug that suits you best.

Older people may be more likely to get side effects than younger people, whatever antidepressant they take. This is because of changes in the body that happen as you get older. Older people may also be on other medications, so there's more chance of side effects from taking more than one drug.

No one knows how likely you are to get side effects. Different studies say different things. But it looks as if the side effects of SSRIs don't bother people quite so much as the side effects you get with TCAs. Overall, people taking TCAs were slightly more likely to drop out of studies because of side effects than people taking SSRIs.12
Comparing different antidepressants

One study compared the side effects of TCAs and SSRIs in people with depression.19
  • TCAs such as amitriptyline, nortriptyline, imipramine, trimipramine and doxepin cause twice as many people to have a dry mouth, constipation and dizziness, compared with SSRIs.
  • SSRIs such as fluoxetine, paroxetine, sertraline and citalopram cause slightly more people to have stomach upsets, anxiety, sleeplessness and headaches than TCAs.
Here are the numbers from the study. Each column shows the percentage of people who got each side effect.

Side effect TCAs SSRIs
Dry mouth 55% 21%
Constipation 22% 10%
Dizziness 23% 13%
Feeling sick 2% 22%
Diarrhea 5% 13%
Anxiety 7% 13%
Agitation 8% 14%
Trouble sleeping 7% 12%
Nervousness 11% 15%
Headache 14% 17%

TCAs are more dangerous than SSRIs if you take an overdose. An overdose of a TCA can cause life-threatening damage to your heart.

SSRIs can make you feel tired, dizzy or generally sick.20 There doesn't seem to be much difference between the drugs in this group.21.
MAOIs and food

The biggest problem with MAOIs, such as phenelzine and tranylcypromine, is that they react with lots of other medicines, foods and alcoholic drinks. If you take an MAOI, eating foods containing the natural chemical tyramine (such as mature cheese) can dangerously raise your blood pressure.22 People taking these drugs have to be careful about what they eat.

MAOIs also react dangerously with most other antidepressants.22.
Venlafaxine

We didn't find any studies reporting the side effects of venlafaxine in people with depression. But studies of people taking venlafaxine for anxiety disorder said it sometimes made them feel nauseous, stopped them sleeping properly and gave them a dry mouth.23 Venlafaxine can also cause sexual problems.24 To learn more, see Side effects of venlafaxine.

Venlafaxine may cause heart problems in some people and may be dangerous if you take an overdose. Talk to your doctor about whether this drug is suitable for you.25
Reboxetine

Reboxetine is a fairly new antidepressant. It's not available in the United States.

More than two-thirds of the people taking reboxetine in studies had side effects.14 26 The most common ones were a dry mouth, trouble sleeping, blurred vision, sweating and constipation. Just over 1 in 10 people said reboxetine made it harder for them to pass urine.8 14 26
Withdrawal symptoms

SSRIs can cause withdrawal symptoms if you stop taking them suddenly or if your dose is reduced. The most common symptoms are dizziness, nausea and vomiting, headaches, a feeling that the room is spinning, and numbness or tingling feelings.27 Other withdrawal symptoms are sweating, anxiety and problems sleeping.25

Paroxetine seems more likely than other SSRIs to cause these problems.27 In one study, nearly two-thirds of people taking paroxetine had withdrawal symptoms when they stopped taking it.28

In another study, 1 in 10 people who stopped taking fluoxetine said they got a runny nose, and 4 in 100 felt sleepy during the day. About 3 in 100 women said they got painful periods.29

Venlafaxine can cause similar withdrawal symptoms.25

Talk to your doctor if you want to stop taking an antidepressant. And never stop your treatment suddenly. You doctor can help you reduce your dose gradually over several weeks to reduce the risk that you'll get withdrawal symptoms.
Antidepressants and children

Some reports suggest that most SSRIs (and a similar drug venlafaxine) might make children and teenagers more likely to harm themselves or think about suicide.30

In the United States, the Food and Drug Administration (FDA), which checks the safety of drugs, has warned that all antidepressants can increase the risk of suicide in children and teenagers.31 Feeling more depressed or thinking about suicide are most likely to happen during the first months of treatment or when the dose is changed.

The FDA has issued this advice after looking at 24 studies that involved some newer antidepressants (SSRIs) and some older drugs. There were 4,400 children included in these studies. They were being treated for depression, obsessive-compulsive disorder or another mental health illness. Some children in the studies were treated with an antidepressant, while others got a pretend treatment (a placebo).

Children who were treated with antidepressants were twice as likely as those taking a placebo to think about suicide. The FDA found that during the first few months of treatment, 4 out of 100 children who took an antidepressant had thoughts of suicide. Among children taking a placebo, 2 out of 100 had thoughts of suicide. None of the children in the studies killed themselves.

If you are a parent or caregiver of a child or teenager who is taking an antidepressant, you should look out for any of the following symptoms in your child:
  • Seeming agitated or irritable
  • Seeming to be getting worse not better
  • Behaving differently or strangely
  • Talking about suicide.
See your doctor if you are at all worried.

If you are a child or teenager taking antidepressants and are worried about any feelings you have, be sure to tell your parents or see your doctor.
Can I take antidepressants if I'm pregnant?

There isn't enough research to say for sure that antidepressants are safe for pregnant women. But:
  • If you take antidepressants late in your pregnancy, your baby may get withdrawal symptoms soon after birth
  • In one study, some mothers who took fluoxetine late in their pregnancy had smaller babies.

Sources for the information on this page:
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  2. Fava GA;Rafanelli C; et al. Prevention of recurrent depression with cognitive behavioral therapy: preliminary findings. Archives of General Psychiatry;55:816-820 1998
  3. Joffe R;Sokolov S; et al. Antidepressant treatment of depression: a metaanalysis. Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie;41:613-616 1996
  4. Lima MS;Moncrieff J A comparison of drugs versus placebo for the treatment of dysthymia. [update in Cochrane Database Syst Rev. 2000;(4):CD0 Cochrane Database of Systematic Reviews 2000
  5. Gill D, Hatcher S. Antidepressants for depression in medical illness (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software.
  6. Furukawa TA, McGuire H, Barbui C. Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: Systematic review. British Medical Journal. 2002;325(7371):991-995.
  7. Williams JW Jr, Mulrow CD, Chiquette E, et al. A systematic review of newer pharmacotherapies for depression in adults: Evidence Annals of Internal Medicine. 2000;132(9):743-756.
  8. Versiani M, Amin M, Chouinard G. Double-blind, placebo-controlled study with reboxetine in inpatients with severe Journal of Clinical Psychopharmacology. 2000;20(1):28-34.
  9. Ban TA, Gaszner P, Aguglia E, et al. Clinical efficacy of reboxetine: A comparative study with desipramine, with methodological considerations. Human Psychopharmacology. 1998;13(SUPPL. 1):S29-S39.
  10. Dubini A, Bosc M, Polin V. Noradrenaline-selective versus serotonin-selective antidepressant therapy: Differential effects on social functioning. Journal of Psychopharmacology. 1997;11(4 SUPPL.):S17-S23.
  11. Geddes JR, Freemantle N, Mason J, et al. Selective serotonin reuptake inhibitors (SSRIs) for depression. In: The Cochrane Library, Issue 2, 2003. Oxford, Update Software.
  12. Anderson IM Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability Journal of Affective Disorders;58:19-36 2000
  13. Smith D, Dempster C, Glanville J, et al. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other British Journal of Psychiatry. 2002;180:396-404.
  14. Massana J, Moller H-J, Burrows GD, et al. Reboxetine: A double-blind comparison with fluoxetine in major depressive disorder. International Clinical Psychopharmacology. 1999;14(2):73-80.
  15. Thase ME;Trivedi MH; et al. MAOIs in the contemporary treatment of depression Neuropsychopharmacology;12:185-219 1995
  16. Geddes JG, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003;361:653-661.
  17. Klysner R, Bent-Hansen J, Hansen HL, et al. Efficacy of citalopram in the prevention of recurrent depression in elderly patients: Placebo-controlled study of maintenance therapy. British Journal of Psychiatry. 2002;181(JULY):29-35.
  18. depression Old Age Depression Interest Group. How long should the elderly take antidepressants? A double-blind placebo-controlled study of continuation/prophylaxis th British Journal of Psychiatry;162:175-182 1993
  19. Trindade E;Menon D. Selective seratonin reuptake inhibitors differ from tricyclic antidepressants in adverse events Ottowa Selective serotonin reuptake inhibitors (SSRIs) for major depression. Part 1. Evaluation of the clinical literature. 1997
  20. Mackay FJ, Dunn NR, Wilton LV et al. A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies. Pharmacoepidemiology and drug safety. 1997;6:235-246.
  21. Price JS;Waller PC; et al. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation o British Journal of Clinical Pharmacology;42:757-763 1996
  22. British National Formulary (BNF) 48. Monoamine-oxidase inhibitors. Available at: http://www.bnf.org (accessed on December 17, 2004).
  23. Rickels K, Plooack MH, Sheehan D, Haskins J Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder Am J Psychiatry 2000;157:968-974 2000
  24. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction Journal of Clinical Psychiatry. 2001 62 Suppl 3:10-21
  25. Committee on Safety of Medicines. Selective Serotonin Reuptake Inhibitors (SSRIs): overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. Available at: http://www.mca.gov.uk/ Accessed on: June 9, 2004. 2004
  26. Berzewski H, Van Moffaert M, Gagiano CA. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive European Neuropsychopharmacology. 1997;7(SUPPL. 1):S37-S47.
  27. Stahl MM;Lindquist M; et al. Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system European Journal of Clinical Pharmacology;53:163-169 1997
  28. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: A randomized clinical trial. Biological Psychiatry. 1998;44(2):77-87.
  29. Zajecka J;Fawcett J; et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study Journal of Clinical Psychopharmacology;18:193-197 1998
  30. Geddes JR, Cipriani A. Selective serotonin reuptake inhibitors. BMJ. 2004;329:809-810.
  31. FDA Public Health Advisory Suicidality in children and adolescents being treated with antidepressant medications October 15, 2004. http://www.fda.gov
  32. Wisner KL;Gelenberg AJ; et al. Pharmacologic treatment of depression during pregnancy. JAMA;282:1264-1269 1999

If you suspect you are suffering from depression, make an appointment with your doctor soon. Prompt, proper treatment of depression can control symptoms and restore your quality of life. With many drug and nondrug options available, having up-to-date, unbiased information is very important.

This article originally appeared on the Consumer Reports Health in December 2004.


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