Tardive Dysphoria: When Antidepressant's Cause Depression

Medical Reviewer

Can long-term treatment with antidepressants contribute to a chronic depressive syndrome? Yes, say some experts. The term tardive dysphoria is now used to describe just such a process.

With rates of depression increasing and the well-documented knowledge that antidepressants provide poor clinical benefits to people with mild-to-moderate depression, the prospect of antidepressants worsening the course of depression over time is concerning. Here are some of the key issues informing the debate:

As things stand maintenance antidepressant therapy is recommended for recurrent major depressive illnesses. Despite this, many people with ongoing antidepressant treatment experience further depressive episodes. In fact around 80 percent of people with major depressive disorder will relapse despite a constant maintenance dose of antidepressants. When this happens the person is considered to be 'treatment-resistant', yet nobody actually knows why it occurs.

In an article about tardive dysphoria, published in Medical Hypotheses, El-Mallakh and colleagues point to the somewhat alarming statistics that the incidence of treatment-resistant depression is increasing. In the early 1990s the incidence of treatment-resistant depression was estimated to be in the region of 10-15 percent, but by 2006 the figures reported were 30-50 percent. They, and others, now believe that antidepressant treatment itself may contribute to a chronic depressive syndrome.

Treatment response to antidepressants is under question. Various studies point to situations where initial response to antidepressants are favorable only to find the response is lost over time (known as tachyphylaxis). Once this initial response is lost it does not appear to return. In one study, patients taking MAOI medication not only didn't respond to subsequent treatment, they reported worse symptoms of depression than before.

Dr Giovanni Fava (1994), was one of the first people to voice open concerns about the potential for antidepressants to worsen depression over time. He provides numerous examples to support his case. For example, in a group of more than 9,000 patients those who took SSRI medication for a year or longer were up to 23 percent more likely to relapse than those who stopped within the first six months. Fava likens antidepressants to antibiotics. Used carefully and for not too long they can be effective.

With antidepressants, the longer they are used the less effective they appear to become and what's worse, there's a chance that depression could become more severe. Fava calls this an "oppositional model of tolerance" which basically means the brain dislikes the disruption caused by antidepressants and compensates in the opposite direction; result, a worsening of the problem the antidepressants tried to solve in the first place.

More and more people take antidepressants than ever before and we have to question where this might lead. Robert Whitaker's thought provoking blog on the topic, published in Psychology Today, closes with the gloomy but relevant observation that here we are, 40 years into antidepressant use, now addressing issues of drug-induced tardive dysphoria. As he says, the brains of teenagers now being prescribed antidepressants will, based on current thinking, develop oppositional tolerance. What then; a lifetime of chronic depression?


Christopher Fisher. Tardive dysphoria is a potential long-term side-effect of antidepressant medication. BMEDReport. http://www.bmedreport.com/archives/24298

Rif S. El-Mallakh., Yonglin Gao., R. Jeannie Roberts. Tardive dysphoria: The role of long term antidepressant use in-inducing chronic depression. Medical Hypotheses 76 (2011) 769-773.

Robert Whitaker. Now antidepressant-induced chronic depression has a name: tardive dysphoria. Psychology Today. Jun 30 (2011) http://www.psychologytoday.com/node/68229