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Johns Hopkins Health Alert

When To Consider A New Antidepressant?

Johns Hopkins Health Alerts | Depression and Anxiety | When To Consider A New Antidepressant

  • Antidepressant medication may require up to eight weeks at a therapeutic dose to produce the full benefit

  • When an antidepressant proves ineffective, a new antidepressant is often selected from a different class of medications

By themselves, antidepressant drugs usually produce a significant improvement by four to six weeks, although it may take up to eight weeks at a therapeutic dose to see the full benefit. According to one study, when an antidepressant that is given at an adequate dosage fails to produce any significant results after the first four weeks, it is unlikely that the drug will work at all. In such cases, the researchers recommend that a new antidepressant be considered.

If the antidepressant produces only partial results after five weeks, they suggest that the antidepressant be continued into the sixth week. If there is no further improvement by then, a new antidepressant can be tried. These trial periods may be somewhat longer for the drugs known as selective serotonin reuptake inhibitors (SSRIs), since this class of drugs was not included in the study.

When an antidepressant proves ineffective, a new antidepressant is often selected from a different class of medications, because drugs in the same class tend to work similarly. In 20% to 50% of patients, adding the drug lithium can help augment the action of an antidepressant. However, this combination increases the risk of side effects and adverse drug interactions. (For this reason, lithium should be prescribed only by a physician knowledgeable in its use.)

If a drug from one class is producing good results but unacceptable side effects, changing to a different drug from the same class may help. If maintenance treatment is no longer required, drugs are discontinued slowly over a period of one to three weeks to avoid withdrawal symptoms. Relapses are most common during the first two months after stopping an antidepressant. Therefore, individuals should remain in contact with their physician during this period. (Should a relapse occur, the same antidepressant that was used successfully the first time often proves effective again.)

Johns Hopkins Health Alerts | Depression and Anxiety | When To Consider A New Antidepressant

Posted in Depression and Anxiety on April 17, 2006
Reviewed June 2008

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Users and editors may post comments here at their own discretion. The views expressed do not constitute medical advice and do not represent the position of Johns Hopkins Medicine or University Health Publishing, which has no responsibility for its content.


I have been on Paxil for over a year and I have noticed that my venous insufficiency has worsened. I was having trouble before I was on Paxil with swelling on my feet. However, after I started on this medication my legs also started to swell and still are swelling. My doctor informed me that it was NOT the medication and then promptly put me on Furosemide 40 mg tablets to reduce swelling. However that has not worked. My legs and feet are so swollen that I cannot wear normal shoes. I suffer also from Stasis Dermatitis and that has definitely not improved due to the excessive swelling. Compression stockings are not doing anything to reduce the swelling either. Please tell me if Paxil causes swelling on the legs and feet when a person is already prone to that condition. I was diagnosed with GAD by my doctor. I know once I get off the Paxil the swelling should go down. If not...well then... I guess I better find a new doctor. Any knowledge of edema being a side effect of Paxil would be appreciated.

Posted by: Heidi | May 9, 2006

From a brief search on Google for Paxil and Edema, I found: http://www.rxlist.com/cgi/generic/parox_ad.htm http://www.mentalhealth.com/drug/p30-p02.html (the charts are easier to read here, I think) which both indicate from the pharma company's own literature, that edema is indeed an 'infrequent' side effect of the medication. Various dermatological side effects are also indicated. I hope this helps you on your road to exploring the difficulties you have related here.

Posted by: Jo | May 12, 2006

Thanks for the info on edema. It give me hope that maybe I can stop this swelling. I have another question. I am on Paxil CR and I cannot cut this pill to reduce the dose. I started skipping a day about a month ago and now have moved to skipping two days. I thought I would stay at this level for another week or so and then try three days without it. Paxil and Paxil CR are different drugs? I have not noticed any electrical shocks in my head. I have noticed some dizziness but nothing to be concerned about. I am sleepy more than usual though. How can I reduce my pill intake when I cannot cut the pill in half? I figure the only option I have is to skip days until over time I can quit altogether. Is there a forum where I can talk about Paxil CR and get support from others who are withdrawing from this drug?

Posted by: Heidi | May 13, 2006

A Google search of Discontinuing use of Paxil gave me 4 results right off the bat that would be good for you to look at, including one site which has some very clear step by step advice, and also user forums.

http://www.medicinenet.com/paroxetine/article.htm also deals with the same subject in a very brief, clear way, with things to watch out for.

Paxil CR is indeed different from regualr Paxil, it is Controlled Release, so the ingredients and the overall effect on the body would be different. Have you talked to your doctor/pharmacist about cutting them up, and if so, about a professional pill cutter? They are not that costly and could be a real help in this situation. Your doctor or a different one might also make different recommendations as to dosage. There is flexibility depending on reasons for taking it, as indicated in the url mentioned above. Best of luck!

Posted by: Jo | May 13, 2006



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